Microbial interactions: ecology in a molecular perspective

Raíssa Mesquita Braga Manuella Nóbrega Dourado Welington Luiz Araújo About the authors

ABSTRACT

The microorganism-microorganism or microorganism-host interactions are the key strategy to colonize and establish in a variety of different environments. These interactions involve all ecological aspects, including physiochemical changes, metabolite exchange, metabolite conversion, signaling, chemotaxis and genetic exchange resulting in genotype selection. In addition, the establishment in the environment depends on the species diversity, since high functional redundancy in the microbial community increases the competitive ability of the community, decreasing the possibility of an invader to establish in this environment. Therefore, these associations are the result of a co-evolution process that leads to the adaptation and specialization, allowing the occupation of different niches, by reducing biotic and abiotic stress or exchanging growth factors and signaling. Microbial interactions occur by the transference of molecular and genetic information, and many mechanisms can be involved in this exchange, such as secondary metabolites, siderophores, quorum sensing system, biofilm formation, and cellular transduction signaling, among others. The ultimate unit of interaction is the gene expression of each organism in response to an environmental (biotic or abiotic) stimulus, which is responsible for the production of molecules involved in these interactions. Therefore, in the present review, we focused on some molecular mechanisms involved in the microbial interaction, not only in microbial-host interaction, which has been exploited by other reviews, but also in the molecular strategy used by different microorganisms in the environment that can modulate the establishment and structuration of the microbial community.

Keywords:
Microbial interaction; Diversity; Microbe-host interaction; Molecular interaction

Introduction

Microbial interactions are crucial for a successful establishment and maintenance of a microbial population. These interactions occur by the environmental recognition followed by transference of molecular and genetic information that include many mechanisms and classes of molecules. These mechanisms allow microorganisms to establish in a community, which depending on the multi-trophic interaction could result in high diversity. The result of this multiple interaction is frequently related to pathogenic or beneficial effect to a host. In humans, for example, the microbial community plays an important role in protection against diseases, caused by microbial pathogens or physiological disturbances. Soils microbial communities also play a major role in protecting plants from diseases and abiotic stresses11 Frey-Klett P, Burlinson P, Deveau A, Barret M, Tarkka M, Sarniguet A. Bacterial-fungal interactions: hyphens between agricultural, clinical, environmental, and food microbiologists. Microbiol Mol Biol Rev. 2011;75:583-609. or increasing nutrient uptake.

Microorganisms are rarely encountered as single species populations in the environment, since studies in different habitats has shown that an enormous richness and abundance variation are usually detected in a small sample, suggesting that microbial interactions are inherent to the establishment of populations in the environment, which includes soil, sediment, animal, and plants, including also fungi and protozoa cells. The many years of coevolution of the different species lead to adaptation and specialization and resulted in a large variety of relationships that can facilitate cohabitation, such as mutualistic and endosymbiotic relationships, or competitive, antagonistic, pathogenic, and parasitic relationships.22 Faust K, Raes J. Microbial interactions: from networks to models. Nat Rev Microbiol. 2012;10:538-550.

Many secondary metabolites have been reported to be involved in the microbial interactions. These compounds are usually bioactive and can perform important functions in ecological interactions. A widely studied mechanism of microbial interaction is quorum sensing, which consists in a stimuli-response system related to cellular concentration. The production of signaling molecules (auto-inducers) allows cells to communicate and respond to the environment in a coordinated way.33 Phelan VV, Liu WT, Pogliano K, Dorrestein PC. Microbial metabolic exchange-the chemotype-to-phenotype link. Nat Chem Biol. 2012;8:26-35. During interaction with the host cells, microbial-associated molecular patterns (PAMP or MAMP - microbial-associated molecular pattern) are conserved throughout different microbial taxon allowing to increase the fitness during interaction with plant or animal cells44 Stuart LM, Paquette N, Boyer L. Effector-triggered versus pattern-triggered immunity: how animals sense pathogens. Nat Rev Immunol. 2013;13:199-206. and regulating the microbial interactions with different hosts (Table 1).

Table 1
Microbial interaction studies.

Much attention has been given to researches on microbial interactions in the human health field. The microbial interactions are crucial for the successful establishment and maintenance of colonization and infection. Additionally, antimicrobial host defenses and environmental factors also play essential roles. Microorganism communication enables the population to collectively regulate the gene expression in response to host and environmental signals, produced by the same or even by different species. This results in a coordinate response in the microbial population, achieving successful pathogenic outcomes that would not be accomplished by individual cells.55 Jimenez PN, Koch G, Thompson JA, Xavier KB, Cool RH, Quax WJ. The multiple signaling systems regulating virulence in Pseudomonas aeruginosa. Microbiol Mol Biol Rev. 2012;76:46-65.

6 Peters BM, Jabra-Rizk MA, O’May GA, Costerton JW, Shirtliff ME. Polymicrobial interactions: impact on pathogenesis and human disease. Clin Microbiol Rev. 2012;25:193-213.
-77 Brickman T, Armstrong S. Temporal signaling and differential expression of Bordetella iron transport systems: the role of ferrimones and positive regulators. Biometals. 2009;22:33-41.

Consequently, knowledge on the mechanisms involved in the microbial interactions can be a key to developing specific agents that can avoid or disturb microorganism communication during infection and consequently act to decrease the defensive and offensive qualities of the pathogen. Thus, the study of these mechanisms can contribute to the understanding of the microbial pathogenesis and to the development of new antimicrobial drugs.55 Jimenez PN, Koch G, Thompson JA, Xavier KB, Cool RH, Quax WJ. The multiple signaling systems regulating virulence in Pseudomonas aeruginosa. Microbiol Mol Biol Rev. 2012;76:46-65.,88 Peleg AY, Hogan DA, Mylonakis E. Medically important bacterial-fungal interactions. Nat Rev Microbiol. 2010;8:340-349.

In addition, microbial interactions occurring in human host can also be benefic and some diseases are often related to imbalances in the healthy microbiota. Therefore, studies on the healthy microbial community in the host are also relevant as it can lead to disease prediction and its appropriate therapies.99 Clemente JC, Ursell LK, Parfrey LW, Knight R. The impact of the gut microbiota on human health: an integrative view. Cell. 2012;148:1258-1270.

10 Knights D, Costello EK, Knight R. Supervised classification of human microbiota. FEMS Microbiol Rev. 2011;35:343-359.
-1111 Virgin HW, Todd JA. Metagenomics and personalized medicine. Cell. 2011;147:44-56.

Microbial interactions also deserve attention from the natural products discovery field. Secondary metabolite clusters that are silent under laboratory growing conditions, can be activated by simulating the natural habitat of the microorganism. It has been reported that co-cultivation with others microorganisms from the same ecosystem can induce the activation of otherwise silent biosynthetic pathways leading to the production and identification of new natural products.1212 Brakhage AA, Schroeckh V. Fungal secondary metabolites - strategies to activate silent gene clusters. Fungal Genet Biol. 2011;48:15-22.

13 Oh DC, Kauffman CA, Jensen PR, Fenical W. Induced production of emericellamides A and B from the marine-derived fungus Emericella sp. in competing co-culture. J Nat Prod. 2007;70:515-520.

14 Schroeckh V, Scherlach K, Nutzmann HW, et al. Intimate bacterial-fungal interaction triggers biosynthesis of archetypal polyketides in Aspergillus nidulans. Proc Natl Acad Sci U S A. 2009;106:14558-14563.

15 Marmann A, Aly AH, Lin W, Wang B, Proksch P. Co-cultivation - a powerful emerging tool for enhancing the chemical diversity of microorganisms. Mar Drugs. 2014;12:1043-1065.
-1616 Netzker T, Fischer J, Weber J, et al. Microbial communication leading to the activation of silent fungal secondary metabolite gene clusters. Front Microbiol. 2015;6:299. Furthermore, this knowledge can also be applied to genetic engineering of phytopathogens antagonists/parasites aiming to an enhanced biological control.1717 Chamoun R, Aliferis KA, Jabaji S. Identification of signatory secondary metabolites during mycoparasitism of Rhizoctonia solani by Stachybotrys elegans. Front Microbiol. 2015;6:353.

In this review, we focused on the molecular mechanisms involved in many microbial interactions, involving intra and interspecies microbial interactions and the microorganism interaction with the host.

Organisms involved

Microorganisms rarely occur as single species populations and are encountered in many hosts/environments, thus there is a large variety of types of microbial interactions concerning the organisms involved. Bacteria-bacteria, fungus-fungus, bacteria-fungus, fungus-plant/animal, bacteria-plant/animal and bacteria-fungus-plant/animal interactions, including parasitic, mutualistic interactions involve many mechanisms that have been described, allowing to develop strategies to manipulate these interactions, which could result in increased host fitness or new metabolite production. According to van Elsas et al.,1818 van Elsas JD, Chiurazzi M, Mallon CA, Elhottova D, Kristufek V, Salles JF. Microbial diversity determines the invasion of soil by a bacterial pathogen. Proc Natl Acad Sci U S A. 2012;109:1159-1164. the establishment of a new species (invader) in an environment depends on the characteristic of the local microbial community. In general, ecosystems that lost species diversity present less ability to resist to an invader, since present more available niche that could be occupied by indigenous species. In addition, during the niche occupation, the invader should interact with species present in this environment.

The mechanisms involved in archaeal interactions are largely unknown, although they are very important in the archaeal communities, production of methane in landfills,1919 Song L, Wang Y, Tang W, Lei Y. Archaeal community diversity in municipal waste landfill sites. Appl Microbiol Biotechnol. 2015;99:6125-6137. archaea in soil and rhizosphere ecosystems,2020 Kent AD, Triplett EW. Microbial communities and their interactions in soil and rhizosphere ecosystems. Annu Rev Microbiol. 2002;56:211-236. thermophilic archaea in bioleaching process,2121 Mikkelsen D, Kappler U, Webb RI, Rasch R, McEwan AG, Sly LI. Visualisation of pyrite leaching by selected thermophilic archaea: nature of microorganism-ore interactions during bioleaching. Hydrometallurgy. 2007;88:143-153. for example. Virus interactions with its host are also very important since viruses are responsible for many diseases in a variety of hosts, and also, modulating the bacterial community by infecting dominant species. Host-virus communication is related to RNA-based mechanisms such as microRNAs.2222 Scaria V, Hariharan M, Maiti S, Pillai B, Brahmachari SK. Host-virus interaction: a new role for microRNAs. Retrovirology. 2006;3:68.,2323 Zhou R, Rana TM. RNA-based mechanisms regulating host-virus interactions. Immunol Rev. 2013;253:97-111. The microorganisms addressed in the present reviewed comprise fungi and bacteria, we did not focus on virus or archaea.

Fungi and bacteria interactions are widely studied, although the molecular mechanisms involved in the interactions are often not completely understood. They interact with a wide range of different organisms - plants, humans and other animals, among others - in different environments, as we describe in this present review, and present many biotechnological applications, such as in food processing, bioremediation, medicine, and biocontrol. In addition, fungal-bacterial association forms a physically and metabolically interdependent conglomerate that presents distinct properties which are biotechnology relevant, especially considering the natural product discovery and synthetic biology field.11 Frey-Klett P, Burlinson P, Deveau A, Barret M, Tarkka M, Sarniguet A. Bacterial-fungal interactions: hyphens between agricultural, clinical, environmental, and food microbiologists. Microbiol Mol Biol Rev. 2011;75:583-609.,2424 Tarkka MT, Sarniguet A, Frey-Klett P. Inter-kingdom encounters: recent advances in molecular bacterium-fungus interactions. Curr Genet. 2009;55:233-243.

There are many microbe-host interactions, which can be related to beneficial or pathogenic interactions in plants and animals. In these interactions, the microbial cells may be found in biofilm or planktonic state, which result in different genetic and physiological states.

Plant-associated microorganisms (endophytic and rhizosphere environment) are able to promote plant growth by producing phytohormones, improving biofertilization, bioremediation, and reducing biotic (disease) and abiotic stress.2525 Mendes R, Garbeva P, Raaijmakers JM. The rhizosphere microbiome: significance of plant beneficial, plant pathogenic, and human pathogenic microorganisms. FEMS Microbiol Rev. 2013;37:634-663. Root-associated endophytes are able to produce phytohormones as auxins and gibberellins promoting plant growth. Considering biofertilization, rhizosphere bacteria are able to fix atmospheric nitrogen, produce siderophore for iron acquisition and mycorrhizal fungi is able to solubilize phosphorus making it available to plant host.2626 Hardoim PR, van Overbeek LS, Berg G, et al. The hidden world within plants: ecological and evolutionary considerations for defining functioning of microbial endophytes. Microbiol Mol Biol R. 2015;79:293-320.

The control of plant stress is exemplified by the production of ACC deaminase that is responsible for the decrease of ethylene levels by cleaving its precursor 1-aminocyclopropane-1-carboxylate (ACC) to ammonia and 2-oxobutanoate, lowering ethylene signaling and this way alleviating plant stress.2727 Hardoim PR, van Overbeek LS, Elsas JD. Properties of bacterial endophytes and their proposed role in plant growth. Trends Microbiol. 2008;16:463-471. A Burkholderia phytofirmans PsJN mutant in the ACC deaminase gene losses the ability to promote root elongation.2828 Sun YL, Cheng ZY, Glick BR. The presence of a 1-aminocyclopropane-1-carboxylate (ACC) deaminase deletion mutation alters the physiology of the endophytic plant growth-promoting bacterium Burkholderia phytofirmans PsJN. Fems Microbiol Lett. 2009;296:131-136. Besides that, the inoculation of a mutualistic bacteria can also affect plant fitness by increasing photosynthetic rate, CO2 assimilation, and chlorophyll content.2929 Naveed M, Hussain MB, Zahir ZA, Mitter B, Sessitsch A. Drought stress amelioration in wheat through inoculation with Burkholderia phytofirmans strain PsJN. Plant Growth Regul. 2014;73:121-131.,3030 Dourado MN, Martins PF, Quecine MC, et al. Burkholderia sp. SCMS54 reduces cadmium toxicity and promotes growth in tomato. Ann Appl Biol. 2013;163:494-507.

The presence genes related to plant growth promoting were addressed in studies comparing the genome of endophytes and pathogens, revealing that pathogens present genes involved in degradation and host invasion while mutualists present genes related to help in stress amelioration, encoding nitrogen fixation proteins and ribulose bisphosphate carboxylase/oxygenase (RubisCO) proteins.2626 Hardoim PR, van Overbeek LS, Berg G, et al. The hidden world within plants: ecological and evolutionary considerations for defining functioning of microbial endophytes. Microbiol Mol Biol R. 2015;79:293-320.

Microbiome interaction with its host

Human

The human microbiome evolves from birth to elderly, resulting in microbial richness and diversity shifts over the whole life, modulating the immune system and physiological and morphological aspects of the host. Although some bacteria may be found in amniotic liquid with or without disease symptoms,3131 DiGiulio DB. Diversity of microbes in amniotic fluid. Semin Fetal Neonatal Med. 2012;17:2-11.

32 DiGiulio DB, Romero R, Amogan HP, et al. Microbial prevalence, diversity and abundance in amniotic fluid during preterm labor: a molecular and culture-based investigation. PLoS ONE. 2008;3:e3056.
-3333 Goldenberg RL, Culhane JF. Infection as a cause of preterm birth. Clin Perinatol. 2003;30:677-700. the development of the human microbiome is studied from birth until this microbial community becomes adult-like. During the whole life, the human microbiome suffers imbalances that have been associated with several kinds of disease, such as asthma, obesity, diabetes, cancer and inflammatory problems in many body sites. The microbiome imbalance is referred as dysbiosis and may result in functional disease or may be caused by a disease or disease treatment. For a better comprehension of the association between intestinal microbial dysbiosis and pediatric diseases the Arrieta et al.,3434 Arrieta MC, Stiemsma LT, Amenyogbe N, Brown EM, Finlay B. The intestinal microbiome in early life: health and disease. Front Immunol. 2014;5:427. review present an important description of the microbial composition and shifts associated with the age.

For the development of this microbial community, the species that will compose this microbiota must show the ability to occupy the available niches and interact with the established microorganism and with host tissues. For this, microbes have to shape their environment by secretion products from their metabolism in a process called niche construction. During this process, the niche is constructed when the microorganisms manage the nutrient available and possible competitors by producing extracellular enzymes, antimicrobial compounds or activating or inhibiting the host immune system.3535 McNally L, Brown SP. Building the microbiome in health and disease: niche construction and social conflict in bacteria. Philos Trans R Soc Lond B Biol Sci. 2015;370. Among this molecules, bacteriocin (peptides produced by a bacterium, that has an immunity mechanisms) active against other bacteria seems to be ubiquitous in bacteria and archaea domain and associated with niche construction, since these ribosomal peptides may work facilitating the introduction and/or dominance of a producer into an already occupied niche, or directly inhibiting competing strains or pathogens during gut colonization of working as signaling peptide (cross-talking) or signaling the host by interaction with receptors for immune system.3636 Dobson A, Cotter PD, Ross RP, Hill C. Bacteriocin production: a probiotic trait? Appl Environ Microbiol. 2012;78:1-6.

Therefore, it is believed that the evolution of a microbial community in the host may be further related to an intrinsic characteristic of this community and the ability of the microbial species to construct their niche. The intrinsic aspects are associated to functional redundancy of the native community, reducing the available niches and the niche construction the ability of the invader to manage the environment (biotic and abiotic characteristics) in a social evolutionary behavior, resulting in a shaped environment that allows the establishment of the microbial colonizer into the host.

During establishment in the gut, microorganisms interact with the host cells expressing adhesive molecules on their surface, promoting interaction with cell receptors and triggering host responses. The most important adhesive structures are pili and fimbrial adhesins in Gram-negative bacteria, but others monomeric surface bound adhesive proteins has been largely identified.3737 Kline KA, Falker S, Dahlberg S, Normark S, Henriques-Normark B. Bacterial adhesins in host-microbe interactions. Cell Host Microbe. 2009;5:580-592. Although the regulation of adhesins has been studied mainly in pathogens, is believed that the same strategy has been used by commensal species. The chaperone-usher pathway has been an important system to assembly pilus adhesins of enteric pathogens, but others such as type IV pili, trimeric autotransporter adhesins (TAA) family, adhesive amyloids (Curli) (Gram-negative bacteria) and Sortase assembled Pili and putative head-stalk-type adhesin (Gram-positive bacteria) are secreted and assembled by Sec-dependent transporter.3737 Kline KA, Falker S, Dahlberg S, Normark S, Henriques-Normark B. Bacterial adhesins in host-microbe interactions. Cell Host Microbe. 2009;5:580-592. These adhesins allow the physical contact between the bacterial cells and host. This interaction mediated by both pilus-associated and non-pilus-associated adhesins with host receptors trigger host inflammatory responses. In addition, this attachment onto eukaryotic cells allows bacteria suppress the host defense by secretion of effector proteins into the host by secretion systems.3737 Kline KA, Falker S, Dahlberg S, Normark S, Henriques-Normark B. Bacterial adhesins in host-microbe interactions. Cell Host Microbe. 2009;5:580-592. Thus, the gut colonization begins rapidly after birth with the microorganism entry by ingestion and keeps going by shaping the environment and attachment onto the host cells or living into the gut lumen.

In addition, during the establishment into the host, gut microbiota may trigger tolerance or inflammatory response in the host. Some Lactobacillus spp. have the ability to induce rheumatoid arthritis by activating TLR (Toll-like receptor) 2 and TLR4 followed by increasing of TH1 and TH17 activity and decreasing TReg-cells function. The production of pro-inflammatory cytokines (IL-17) and endogen TLR4 agonist mediate joint inflammation by stimulating plasma cells to produce arthritogenic autoantibodies. However, some commensal bacteria, such as Bacteroides fragilis are able to activate pro-tolerogenic machinery, the PSA, a cell wall component, induce activation of TReg-cells and IL-10 production and repression of TH17-cell, avoiding uncontrolled inflammation.3838 Scher JU, Abramson SB. The microbiome and rheumatoid arthritis. Nat Rev Rheumatol. 2011;7:569-578. Cell wall components, such as peptidoglycans (PGN) may also spread into the host and be recognized by pattern recognition receptor (PRRs). The recognition of this PGN may trigger, not only a host immune response, but also host metabolism and behavior.3939 Wheeler R, Chevalier G, Eberl G, Gomperts Boneca I. The biology of bacterial peptidoglycans and their impact on host immunity and physiology. Cell Microbiol. 2014;16:1014-1023.

During bacterial growth, PGN is degraded and although bacterial PGN recycling pathway tries to reduce the bioavailability of soluble fragments (preventing detection by the host)3939 Wheeler R, Chevalier G, Eberl G, Gomperts Boneca I. The biology of bacterial peptidoglycans and their impact on host immunity and physiology. Cell Microbiol. 2014;16:1014-1023. fragments (muropeptides) could disseminate systemically, activating receptors far from the gut. In fact, receptors (Nod1 and Nod2) that recognize these PGN fragments are broadly distributed into the human and animal bodies. In addition, in rats that present sleep deprivation, the bacterial translocation from the intestine to the mesenteric lymph nodes was observed.4040 Everson CA, Toth LA. Systemic bacterial invasion induced by sleep deprivation. Am J Physiol Regul Integr Comp Physiol. 2000;278:R905-R916. and in previous studies, it was observed that muramyl peptides may induce a somnogenic response after brain ventricule4141 Krueger JM, Pappenheimer JR, Karnovsky ML. The composition of sleep-promoting factor isolated from human urine. J Biol Chem. 1982;257:1664-1669. or intravenous or injection.4242 Johannsen L, Toth LA, Rosenthal RS, et al. Somnogenic, pyrogenic, and hematologic effects of bacterial peptidoglycan. Am J Physiol. 1990;258:R182-R186. These results suggest that sleep deprivation could induce bacterial translocation, which could be a source of muramyl peptides for sleeping induction.3939 Wheeler R, Chevalier G, Eberl G, Gomperts Boneca I. The biology of bacterial peptidoglycans and their impact on host immunity and physiology. Cell Microbiol. 2014;16:1014-1023. These results suggest that the host behavior could modulate the interaction with the microbial community, which in turn contribute to shifts in the host physiology.

Soil and plant

All organisms are inhabited by microorganisms including archaea, bacteria, fungi and viruses; this microbiota presents a key role in host health and development.4343 Berg G, Rybakova D, Grube M, Koberl M. The plant microbiome explored: implications for experimental botany. J Exp Bot. 2016;67:995-1002.,4444 Mendes R, Raaijmakers JM. Cross-kingdom similarities in microbiome functions. ISME J. 2015;9:1905-1907. The microbiome associated with plants is considered its second genome. It is determinants for plant health, growth, fitness and consequently productivity.4545 Lakshmanan V, Selvaraj G, Bais HP. Functional soil microbiome: belowground solutions to an aboveground problem. Plant Physiol. 2014;166:689-700. Where each environment associated with the plant: rhizosphere, endosphere, and phyllosphere present a specific microbial community with specific functions.4343 Berg G, Rybakova D, Grube M, Koberl M. The plant microbiome explored: implications for experimental botany. J Exp Bot. 2016;67:995-1002.

These culture-independent methods show that plant microbiome can reach densities greater than the number of plant cells and also greater expressed genes than the host cells. Metagenomics analysis using next-generation sequencing technologies shows that only 5% of bacteria have been cultured by current methods, revealing how many microorganisms and its functions remains unknown.2525 Mendes R, Garbeva P, Raaijmakers JM. The rhizosphere microbiome: significance of plant beneficial, plant pathogenic, and human pathogenic microorganisms. FEMS Microbiol Rev. 2013;37:634-663.

The first step in plant-microbe interaction is microbial recognition of plant exudates in the soil. There is a hypothesis that plants are able to recruit microorganism by plant exudates, which are composed of amino acids, carbohydrates and organic acids that can vary according to the plant and its biotic or abiotic conditions.4646 Haldar S, Sengupta S. Plant-microbe cross-talk in the rhizosphere: insight and biotechnological potential. Open Microbiol J. 2015;9:1-7. Different plants select specific microbial communities as reported by Berg et al.,4343 Berg G, Rybakova D, Grube M, Koberl M. The plant microbiome explored: implications for experimental botany. J Exp Bot. 2016;67:995-1002. when comparing rhizosphere colonization of two medicinal plants: chamomile (Matricaria chamomilla) and nightshade (Solanum distichum), despite being cultivated under similar conditions, they presented different structural (analyzing 16S rRNA genes) and functional (analyzing nitrogen fixing - nifH genes) microbial community. Moreover, plant exudate of the same plant varies according to plant developmental stages selecting specific microbial communities.4747 Chaparro JM, Badri DV, Bakker MG, Sugiyama A, Manter DK, Vivanco JM. Root exudation of phytochemicals in Arabidopsis follows specific patterns that are developmentally programmed and correlate with soil microbial functions. PLoS ONE. 2013;8:e55731. Researchers already identified some plant exudate compounds responsible for specific interactions such as flavonoids in Legume-Rhizobia4848 Peters NK, Frost JW, Long SR. A plant flavone, luteolin, induces expression of rhizobium-meliloti nodulation genes. Science. 1986;233:977-980. and Strigolactone as a signal molecule for arbuscular mycorrhizal fungi (AMF).4949 Akiyama K, Matsuzaki K, Hayashi H. Plant sesquiterpenes induce hyphal branching in arbuscular mycorrhizal fungi. Nature. 2005;435:824-827.

Reinhold-Hurek et al.,5050 Reinhold-Hurek B, Bunger W, Burbano CS, Sabale M, Hurek T. Roots shaping their microbiome: global hotspots for microbial activity. Annu Rev Phytopathol. 2015;53:403-424. proposed a model for microorganism colonization. In bulk soil, the microbial community presents a great diversity and is influenced only by soil type and environmental factors. Getting closer to plant roots (rhizosphere), where there are root exudates, there are fewer species and a more specialized community. And only a few species are able to enter plant root and establish in the plant. Furthermore, after entering the plant, microbial community varies among the different organs: top leaves, fruits, bottom leaves, flowers, stems and roots.5151 Ottesen AR, Pena AG, White JR, et al. Baseline survey of the anatomical microbial ecology of an important food plant: Solanum lycopersicum (tomato). BMC Microbiol. 2013;:13.

Mutualistic microorganisms can protect plants from pathogen either by inducing plant resistance or by antibiosis. The induced systemic resistance (ISR) in plants leads to high tolerance to pathogens. There are soils that even if there is the pathogen the disease does not occur, the mechanisms of these disease-suppressive are still being investigated. In this way, Mendes et al.,5252 Mendes R, Kruijt M, de Bruijn I, et al. Deciphering the rhizosphere microbiome for disease-suppressive bacteria. Science. 2011;332:1097-1100. analyzed the microbiome of a soil suppressive to the fungal pathogen Rhizoctonia solani that causes damping off in several agricultural crops. Using a 16S rDNA oligonucleotide microarray (PhyloChip) they were able to identify more than 33,000 bacterial and archaeal taxa in the sugar beet seedlings rhizosphere grown in suppressive soil and in conductive soils. These analyses revealed the bacterial groups present only in the suppressive soil. The authors reported that γ-Proteobacteria, especially Pseudomonadaceae, were all more abundant in suppressive soil than in conducive soil, focusing thereby in this bacterial group. Using random transposon mutagenesis technic in Pseudomonas sp. they were able to identified genes responsible for the biosynthesis of an antifungal: nine-amino acid chlorinated lipopeptide produced by Pseudomonas sp. and controls the pathogen.

From the same PhyloChip diversity analysis, Cordovez et al.,5353 Cordovez V, Carrion VJ, Etalo DW, et al. Diversity and functions of volatile organic compounds produced by Streptomyces from a disease-suppressive soil. Front Microbiol. 2015;6:1081. identified other antifungal, this time produced by rhizosphere-associated streptomycetes. Theses Streptomyces isolates were able to produce chemically diverse volatile organic compounds (VOCs) with an antifungal activity as well as plant growth-promoting properties. Showing that different bacteria groups can have similar roles in the same environment. Another example was reported by Ardanov et al.,5454 Ardanov P, Sessitsch A, Haggman H, Kozyrovska N, Pirttila AM. Methylobacterium-induced endophyte community changes correspond with protection of plants against pathogen attack. PLoS ONE. 2012;7:e46802. who showed that the inoculation of Methylobacterium strains also protected plants against pathogen attack and affected endophyte communities. Therefore, using this concept, researchers started inoculating plants with a pool of microorganism with complementary traits, for example with different mechanisms of control, however, it is a challenge to find the right players to be inoculated.2525 Mendes R, Garbeva P, Raaijmakers JM. The rhizosphere microbiome: significance of plant beneficial, plant pathogenic, and human pathogenic microorganisms. FEMS Microbiol Rev. 2013;37:634-663.

In order to define which microorganisms should be inoculated several approaches were used. The first approach seeks to define a core microbiome of a healthy host, or understand the function of microbiomes by sequencing approach, that can be followed by experiments on gnotobiotic host manipulating the microbiome with a selection factor (for example antibiotics, salinity, and U.V. light) or transferring microbiomes between hosts.5555 Mueller UG, Sachs JL. Engineering microbiomes to improve plant and animal health. Trends Microbiol. 2015;23:606-617.

In this way, researchers are starting to study “microbiome engineering”, modulating microbial community. This modulation can occur either by performing plant breeding programs selecting a beneficial interaction between plant lines and rhizosphere microbiome or by redirect rhizosphere microbiome by stimulating or introducing beneficial microorganisms.2525 Mendes R, Garbeva P, Raaijmakers JM. The rhizosphere microbiome: significance of plant beneficial, plant pathogenic, and human pathogenic microorganisms. FEMS Microbiol Rev. 2013;37:634-663.,5555 Mueller UG, Sachs JL. Engineering microbiomes to improve plant and animal health. Trends Microbiol. 2015;23:606-617. The microbiome engineering can occur by altering ecological processes such as modulation in community diversity and structure changing microbe-interaction networks and by altering the evolutionary processes which include extinction of microbial species in the microbiome, horizontal gene transfer, and mutations that can restructure microbial genomes.5555 Mueller UG, Sachs JL. Engineering microbiomes to improve plant and animal health. Trends Microbiol. 2015;23:606-617.

Summarizing, plant phenotype is the sum of plant response to the environment and to the present microbiome (including endophytes and pathogens), this microbiome also responds to the environment and interacts with each other.2626 Hardoim PR, van Overbeek LS, Berg G, et al. The hidden world within plants: ecological and evolutionary considerations for defining functioning of microbial endophytes. Microbiol Mol Biol R. 2015;79:293-320. Mendes and Raaijmakers4444 Mendes R, Raaijmakers JM. Cross-kingdom similarities in microbiome functions. ISME J. 2015;9:1905-1907. suggest a similarity between gut and plant rhizosphere microbiomes. They are both open systems, with a gradient of oxygen, water, and pH resulting in a large number and diversity of microorganism due to the different existing conditions. There are differences between gut and plant rhizosphere microbiome composition, therefore there are some similarities related to nutrient acquisition, immune system modulation and protection against infections. Berg et al.,5656 Berg G, Krause R, Mendes R. Cross-kingdom similarities in microbiome ecology and biocontrol of pathogens. Front Microbiol. 2015;6:1311. point seven the similarities between host-associated microbiome ecology, among them: different abiotic conditions shape the structure of microbial communities; host and its microbiome co-evolute; core microbiome can be transmitted vertically; during life cycle the microbiome structure varies; host-associated microbiomes are composed of bacteria, archaea, and eukaryotic microorganisms; functional diversity is key in a microbiome; microbial diversity is lost by Human interventions.

Secondary metabolism

Microorganisms produce a large variety of compounds known as secondary metabolites that do not play an essential role in growth, development, and reproduction of the producing organism.5757 Keller NP, Turner G, Bennett JW. Fungal secondary metabolism - from biochemistry to genomics. Nat Rev Microbiol. 2005;3:937-947. Nevertheless, these metabolites are often bioactive compounds and can perform important functions in defense, competition, signaling, and ecological interactions.5858 Yin W, Keller NP. Transcriptional regulatory elements in fungal secondary metabolism. J Microbiol. 2011;49:329-339.,5959 Demain AL, Fang A. The natural functions of secondary metabolites. Adv Biochem Eng Biotechnol. 2000;69:1-39.

To establish a microbial interaction network, microorganisms usually respond by metabolic exchange, which leads to complex regulatory responses involving the biosynthesis of secondary metabolites. These interactions can be parasitic, antagonistic, or competitive and the metabolites involved and their functions have been specially studied recently as a result of the advent of tools such as metabolomics and imaging mass spectrometry (IMS) technology.1717 Chamoun R, Aliferis KA, Jabaji S. Identification of signatory secondary metabolites during mycoparasitism of Rhizoctonia solani by Stachybotrys elegans. Front Microbiol. 2015;6:353.,6060 Bilyk O, Luzhetskyy A. Metabolic engineering of natural product biosynthesis in actinobacteria. Curr Opin Biotechnol. 2016;42:98-107.,6161 Tata A, Perez C, Campos ML, Bayfield MA, Eberlin MN, Ifa DR. Imprint desorption electrospray ionization mass spectrometry imaging for monitoring secondary metabolites production during antagonistic interaction of fungi. Anal Chem. 2015;87:12298-12304.

Siderophores are related to competitive and cooperative microbial interactions and can also play other roles, such as signaling and antibiotic activity.6262 Johnstone TC, Nolan EM. Beyond iron: non-classical biological functions of bacterial siderophores. Dalton Trans. 2015;44:6320-6339. Hopanoids play an important role in bacterial interaction, conferring tolerance and improving the adaptation of bacteria in different environments.6363 Schmerk CL, Welander PV, Hamad MA, et al. Elucidation of the Burkholderia cenocepacia hopanoid biosynthesis pathway uncovers functions for conserved proteins in hopanoid-producing bacteria. Environ Microbiol. 2015;17:735-750.

64 Malott RJ, Steen-Kinnaird BR, Lee TD, Speert DP. Identification of hopanoid biosynthesis genes involved in polymyxin resistance in Burkholderia multivorans. Antimicrob Agents Chemother. 2012;56:464-471.
-6565 Lopez-Lara IM, Sohlenkamp C, Geiger O. Membrane lipids in plant-associated bacteria: their biosyntheses and possible functions. Mol Plant Microbe Interact. 2003;16:567-579. In fungi, the compounds differentially regulated in an interaction are often bioactive secondary metabolites, such as diketopiperazines, trichothecenes, atranones, and polyketides.1414 Schroeckh V, Scherlach K, Nutzmann HW, et al. Intimate bacterial-fungal interaction triggers biosynthesis of archetypal polyketides in Aspergillus nidulans. Proc Natl Acad Sci U S A. 2009;106:14558-14563.,1717 Chamoun R, Aliferis KA, Jabaji S. Identification of signatory secondary metabolites during mycoparasitism of Rhizoctonia solani by Stachybotrys elegans. Front Microbiol. 2015;6:353. Nevertheless, there is still a lot to understand about the mechanisms involved and the role of many secondary metabolites and genes differentially expressed during the interaction. In this section, we present examples of studies on secondary metabolites involved in different types of microbial interactions.

Endophyte-phytopathogen-plant interaction

The metabolites and mechanisms involved in the interactions between endophyte and phytopathogen and host plant are still very unclear and are predicted to involve many secondary metabolites. Endophytic fungi are known to produce a large variety of bioactive secondary metabolites6666 Prakash V. Endophytic fungi as resource of bioactive compounds. Int J Pharm Bio Sci. 2015;6:887-898.,6767 Suryanarayanan TS, Shaanker RU. Fungal endophytes - biology and bioprospecting preface. Curr Sci India. 2015;109:37-38. that are probably related to the endophyte complex interactions with the host and the phytopathogens and can perform important ecological functions, for example, in the plant development (as growth promoters) and in defense, acting against phytopathogens.6868 Schulz B, Boyle C. The endophytic continuum. Mycol Res. 2005;109:661-686.,6969 Strobel GA. Endophytes as sources of bioactive products. Microbes Infect. 2003;5:535-544.

This interaction has been studied in co-cultures of the phytopathogen Moniliophthora roreri and the endophyte Trichoderma harzianum that cohabit in cacao plants.6161 Tata A, Perez C, Campos ML, Bayfield MA, Eberlin MN, Ifa DR. Imprint desorption electrospray ionization mass spectrometry imaging for monitoring secondary metabolites production during antagonistic interaction of fungi. Anal Chem. 2015;87:12298-12304.T. harzianum is extensively used as a biocontrol agent and has known ability to antagonize M. roreri. They identified four secondary metabolites (T39 butenolide, harzianolide, sorbicillinol, and an unknown substance) which production was dependent on the phytopathogen presence and was spatially localized in the interaction zone.6161 Tata A, Perez C, Campos ML, Bayfield MA, Eberlin MN, Ifa DR. Imprint desorption electrospray ionization mass spectrometry imaging for monitoring secondary metabolites production during antagonistic interaction of fungi. Anal Chem. 2015;87:12298-12304. T39 butenolide and harzianolide have been reported to have antifungal activity. Sorbicillinol is an intermediate in the biosynthesis of bisorbicillinoids, a family of secondary metabolites which present diverse activities.7070 Abe N, Sugimoto O, Arakawa T, Tanji K, Hirota A. Sorbicillinol, a key intermediate of bisorbicillinoid biosynthesis in Trichoderma sp USF-2690. Biosci Biotechnol Biochem. 2001;65:2271-2279.

Trichoderma atroviride, commonly used as a biocontrol agent, produces acetic acid-related indoles compounds that may stimulate plant growth. Colonization of Arabidopsis roots by T. atroviride promotes growth and enhances systemic disease resistance conferring resistance against hemibiotrophic and necrotrophic phytopathogens.7171 Salas-Marina MA, Silva-Flores MA, Uresti-Rivera EE, Castro-Longoria E, Herrera-Estrella A, Casas-Flores S. Colonization of Arabidopsis roots by Trichoderma atroviride promotes growth and enhances systemic disease resistance through jasmonic acid/ethylene and salicylic acid pathways. Eur J Plant Pathol. 2011;131:15-26.

Other co-cultured studies were performed with bacteria. Araújo et al.,7272 Araujo WL, Marcon J, Maccheroni W, Van Elsas JD, Van Vuurde JW, Azevedo JL. Diversity of endophytic bacterial populations and their interaction with Xylella fastidiosa in citrus plants. Appl Environ Microbiol. 2002;68:4906-4914. isolated a great number of Methylobacterium strains from asymptomatic citrus plants (with Xylella fastidiosa but without disease), then Lacava et al.,7373 Lacava PT, Araujo WL, Marcon J, Maccheroni W, Azevedo JL. Interaction between endophytic bacteria from citrus plants and the phytopathogenic bacteria Xylella fastidiosa, causal agent of citrus-variegated chlorosis. Lett Appl Microbiol. 2004;39:55-59. showed that Methylobacterium mesophilicum SR1.6/6 and Curtobacterium sp. ER1.6/6 isolated from health and asymptomatic plants inhibited the growth of the phytopathogen Xylella fastidiosa, the causal agent of citrus variegated chlorosis. Moreover, transcriptional profile of Xylella fastidiosa was evaluated during in vitro co-cultivation with a citrus endophytic strain of Methylobacterium mesophilicum. It was shown that genes related to growth, such as genes involved in DNA replication and protein synthesis, were down-regulated. While genes related to energy production, stress, transport, and motility, such as fumarate hydratase, dihydrolipoamide dehydrogenase (Krebs cycle), pilY transporter, clpP peptidase, acriflavin resistance, and toluene tolerance genes, were up-regulated.7474 Dourado MN, Santos DS, Nunes LR, Costa de Oliveira RL, de Oliveira MV, Araujo WL. Differential gene expression in Xylella fastidiosa 9a5c during co-cultivation with the endophytic bacterium Methylobacterium mesophilicum SR1.6/6. J Basic Microbiol. 2015;55:1357-1366.

Another approach to study endophyte-phytopathogen-plant interaction is based on the genome sequencing and transposon mutagenesis of an endophyte strain of Burkholderia seminalis, which suppress orchid leaf necrosis by Burkholderia gladioli, revealed eight loci related to biological control. A wcb cluster related to the synthesis of extracellular polysaccharides of the bacterial capsule was identified.7575 Araujo WL, Creason AL, Mano ET, et al. Genome sequencing and transposon mutagenesis of Burkholderia seminalis TC3.4.2R3 identify genes contributing to suppression of orchid necrosis caused by B. gladioli. Mol Plant Microbe Interact. 2016;29:435-446. Extracellular polysaccharides are known to be key factors in bacterial-host interactions.7676 Kim HS, Schell MA, Yu Y, et al. Bacterial genome adaptation to niches: divergence of the potential virulence genes in three Burkholderia species of different survival strategies. BMC Genom. 2005;6:174.,7777 Sim BM, Chantratita N, Ooi WF, et al. Genomic acquisition of a capsular polysaccharide virulence cluster by non-pathogenic Burkholderia isolates. Genome Biol. 2010;11:R89. In addition, genes clusters putatively related to indole-acetic acid and ethylene biosynthesis were identified in the sequenced genome of the endophyte strain, suggesting that this strain might interact with the plant by altering hormone metabolism.7575 Araujo WL, Creason AL, Mano ET, et al. Genome sequencing and transposon mutagenesis of Burkholderia seminalis TC3.4.2R3 identify genes contributing to suppression of orchid necrosis caused by B. gladioli. Mol Plant Microbe Interact. 2016;29:435-446.

Hopanoid

Hopanoids compose the cell membrane of some bacteria,7878 Bradley AS, Pearson A, Sáenz JP, Marx CJ. Adenosylhopane: the first intermediate in hopanoid side chain biosynthesis. Org Geochem. 2010;41:1075-1081. presenting the same function of eukaryotes cholesterol. They are responsible for stabilization of the membrane and regulates its fluidity and permeability.7979 Welander PV, Hunter RC, Zhang L, Sessions AL, Summons RE, Newman DK. Hopanoids play a role in membrane integrity and pH homeostasis in Rhodopseudomonas palustris TIE-1. J Bacteriol. 2009;191:6145-6156. Experiments that knockout biosynthesis genes such as hnpF (squalene hopene cyclase-shc) gene shows that the absence of hopanoids does not influence bacterial growth,7979 Welander PV, Hunter RC, Zhang L, Sessions AL, Summons RE, Newman DK. Hopanoids play a role in membrane integrity and pH homeostasis in Rhodopseudomonas palustris TIE-1. J Bacteriol. 2009;191:6145-6156.,8080 Seipke RF, Loria R. Hopanoids are not essential for growth of Streptomyces scabies 87-22. J Bacteriol. 2009;191:5216-5223. but affects tolerance to several stress conditions, such as extremely acidic environments8181 Jones DS, Albrecht HL, Dawson KS, et al. Community genomic analysis of an extremely acidophilic sulfur-oxidizing biofilm. ISME J. 2012;6:158-170.; toxic compounds as dichloromethane (DCM)8282 Muller EE, Hourcade E, Louhichi-Jelail Y, Hammann P, Vuilleumier S, Bringel F. Functional genomics of dichloromethane utilization in Methylobacterium extorquens DM4. Environ Microbiol. 2011;13:2518-2535.; it also affects the resistance to antibiotics6464 Malott RJ, Steen-Kinnaird BR, Lee TD, Speert DP. Identification of hopanoid biosynthesis genes involved in polymyxin resistance in Burkholderia multivorans. Antimicrob Agents Chemother. 2012;56:464-471. and antimicrobial lipopeptide6363 Schmerk CL, Welander PV, Hamad MA, et al. Elucidation of the Burkholderia cenocepacia hopanoid biosynthesis pathway uncovers functions for conserved proteins in hopanoid-producing bacteria. Environ Microbiol. 2015;17:735-750.; playing a role in multidrug transport8383 Saenz JP, Grosser D, Bradley AS, et al. Hopanoids as functional analogues of cholesterol in bacterial membranes. Proc Natl Acad Sci U S A. 2015;112:11971-11976. and bacterial motility.8484 Schmerk CL, Bernards MA, Valvano MA. Hopanoid production is required for low-pH tolerance, antimicrobial resistance, and motility in Burkholderia cenocepacia. J Bacteriol. 2011;193:6712-6723.

Hopanoids act increasing bacteria tolerance to adverse environments, conferring resistance to stress conditions including extreme pH and temperature, and exposure to detergents and antibiotics.6363 Schmerk CL, Welander PV, Hamad MA, et al. Elucidation of the Burkholderia cenocepacia hopanoid biosynthesis pathway uncovers functions for conserved proteins in hopanoid-producing bacteria. Environ Microbiol. 2015;17:735-750.,6464 Malott RJ, Steen-Kinnaird BR, Lee TD, Speert DP. Identification of hopanoid biosynthesis genes involved in polymyxin resistance in Burkholderia multivorans. Antimicrob Agents Chemother. 2012;56:464-471. In this way, hopanoids may be involved in bacteria-plant interaction, being responsible for adaptation of bacteria in aerobic micro-environment and low pH culture medium6565 Lopez-Lara IM, Sohlenkamp C, Geiger O. Membrane lipids in plant-associated bacteria: their biosyntheses and possible functions. Mol Plant Microbe Interact. 2003;16:567-579.; as well as involved in nitrogen metabolism in Frankia sp.8585 Nalin R, Putra SR, Domenach AM, Rohmer M, Gourbiere F, Berry AM. High hopanoid/total lipids ratio in Frankia mycelia is not related to the nitrogen status. Microbiology. 2000;146:3013-3019. For example, a type of hopanoids produced by the nitrogen-fixing bacteria Bradyrhizobium diazoefficiens is essential for its symbiosis with the host Aeschynomene afraspera, a tropical legume. In this case, the synthesis of C35 hopanoids is related to evasion of plant defense, utilization of host photosynthates, and nitrogen fixation.8686 Kulkarni G, Busset N, Molinaro A, et al. Specific hopanoid classes differentially affect free-living and symbiotic states of Bradyrhizobium diazoefficiens. MBio. 2015;6:e01251-e01315.

Parasitic interaction

The study of the mycoparasitic interaction between Stachybotrys elegans and Rhizoctonia solani revealed many secondary metabolites differentially expressed in the interaction.1717 Chamoun R, Aliferis KA, Jabaji S. Identification of signatory secondary metabolites during mycoparasitism of Rhizoctonia solani by Stachybotrys elegans. Front Microbiol. 2015;6:353. During the interaction, S. elegans produces cell wall degrading enzymes and express genes associated with parasitism8787 Morissette DC, Driscoll BT, Jabaji-Hare S. Molecular cloning, characterization, and expression of a cDNA encoding an endochitinase gene from the mycoparasite Stachybotrys elegans. Fungal Genet Biol. 2003;39:276-285.,8888 Morissette DC, Dauch A, Beech R, Masson L, Brousseau R, Jabaji-Hare S. Isolation of mycoparasitic-related transcripts by SSH during interaction of the mycoparasite Stachybotrys elegans with its host Rhizoctonia solani. Curr Genet. 2008;53:67-80. while R. solani responds with an elevated level of the pyridoxal reductase-encoding gene.8989 Chamoun R, Jabaji S. Expression of genes of Rhizoctonia solani and the biocontrol Stachybotrys elegans during mycoparasitism of hyphae and sclerotia. Mycologia. 2011;103:483-493. A metabolomic study showed the profile of the induced secondary metabolites during the interaction. It was showed a significant effect of the mycoparasite on R. solani metabolism, the biosynthesis of many antimicrobial compounds were down-regulated, possibly as a result of the interaction, and only a few diketopiperazines were induced.1717 Chamoun R, Aliferis KA, Jabaji S. Identification of signatory secondary metabolites during mycoparasitism of Rhizoctonia solani by Stachybotrys elegans. Front Microbiol. 2015;6:353. Diketopiperazines are known to have antimicrobial properties, among others biological activities.9090 Martins MB, Carvalho I. Diketopiperazines: biological activity and synthesis. Tetrahedron. 2007;63:9923-9932. The mycoparasite S. elegans produced several mycotoxins, mainly trichothecenes and atranones. They hypothesized that the trichothecenes were triggered by R. solani and were responsible for the alteration in its metabolism, growth, and development.1717 Chamoun R, Aliferis KA, Jabaji S. Identification of signatory secondary metabolites during mycoparasitism of Rhizoctonia solani by Stachybotrys elegans. Front Microbiol. 2015;6:353. Trichothecenes are a major class of mycotoxins and have been reported to inhibit eukaryotic protein biosynthesis and generate oxidative stress.9191 McCormick SP, Stanley AM, Stover NA, Alexander NJ. Trichothecenes: from simple to complex mycotoxins. Toxins. 2011;3:802-814.

Microbial communities interaction

Actinomycetes are noteworthy as producers of many natural products with a wide range of bioactivities.6060 Bilyk O, Luzhetskyy A. Metabolic engineering of natural product biosynthesis in actinobacteria. Curr Opin Biotechnol. 2016;42:98-107. A study on Streptomyces coelicolor interacting with other actinomycetes showed that most of the compounds produced in each interaction were unique, revealing a differential response in each case. Many unknown molecules and an extended family of acyl-desferrioxamine siderophores never described before in S. coelicolor were identified. They identified 227 compounds differentially produced in interactions; half of these were known metabolites: prodiginines, actinorhodins, coelichelins, and acyl-desferrioxamines. Thus, actinomycetes interspecies interaction seems to be very specific and complex.9292 Traxler MF, Watrous JD, Alexandrov T, Dorrestein PC, Kolter R. Interspecies interactions stimulate diversification of the Streptomyces coelicolor secreted metabolome. MBio. 2013;4.

It has been shown that fungal-bacterial interactions can lead to the production of specific fungal secondary metabolites and not only diffusible compounds act in this communication, but there is also a contribution from physical interaction.1414 Schroeckh V, Scherlach K, Nutzmann HW, et al. Intimate bacterial-fungal interaction triggers biosynthesis of archetypal polyketides in Aspergillus nidulans. Proc Natl Acad Sci U S A. 2009;106:14558-14563. Schroeckh et al.,1414 Schroeckh V, Scherlach K, Nutzmann HW, et al. Intimate bacterial-fungal interaction triggers biosynthesis of archetypal polyketides in Aspergillus nidulans. Proc Natl Acad Sci U S A. 2009;106:14558-14563. demonstrated that an intimate physical interaction between Aspergillus nidulans and the actinomycete Streptomyces rapamycinicus leads to the activation of fungal secondary metabolite genes related to the production of aromatic polyketides, which were otherwise silent. A PKS gene required for the biosynthesis of the archetypal polyketide orsellinic acid, lecanoric acid (typical lichen metabolite), and the compounds F-9775A and F-9775B (cathepsin K inhibitors) was identified.1414 Schroeckh V, Scherlach K, Nutzmann HW, et al. Intimate bacterial-fungal interaction triggers biosynthesis of archetypal polyketides in Aspergillus nidulans. Proc Natl Acad Sci U S A. 2009;106:14558-14563. It was later reported that alterations in fungal histone acetylation via the Saga/Ada complex are triggered by the actinomycete leading to the induction of the otherwise silent PKS cluster. This result shows that bacteria can trigger alterations of histone acetylation in fungi.9393 Nutzmann HW, Reyes-Dominguez Y, Scherlach K, et al. Bacteria-induced natural product formation in the fungus Aspergillus nidulans requires Saga/Ada-mediated histone acetylation. Proc Natl Acad Sci U S A. 2011;108:14282-14287.

Siderophore

The production and acquisition of siderophores by microorganisms is a crucial mechanism to obtain iron. Many microorganisms secrete siderophores in the environment that when loaded are recognized by cell surface receptors and then transported into the microbial cell.9494 Faraldo-Gomez JD, Sansom MS. Acquisition of siderophores in gram-negative bacteria. Nat Rev Mol Cell Biol. 2003;4:105-116. Thus, they are related to competitive and cooperative microbial interactions. In addition, many siderophores can also present other functions, for example, they can function as sequesters of a variety of metals and even heavy metal toxins, as signaling molecules, as agents in regulating oxidative stress, and as antibiotics, which were reviewed by Johnstone and Nolan.6262 Johnstone TC, Nolan EM. Beyond iron: non-classical biological functions of bacterial siderophores. Dalton Trans. 2015;44:6320-6339.

In some Pseudomonas species, a group of siderophores called pyoverdines is essential to infection and biofilm formation, probably helping to regulate bacterial growth.9595 Visca P, Imperi F, Lamont IL. Pyoverdine siderophores: from biogenesis to biosignificance. Trends Microbiol. 2007;15:22-30. Pyoverdines have been reported to act as signaling molecules triggering a cascade that results in the production of several virulence factors, such as exotoxin A, PrpL endoprotease, and pyoverdine itself.9696 Lamont IL, Beare PA, Ochsner U, Vasil AI, Vasil ML. Siderophore-mediated signaling regulates virulence factor production in Pseudomonas aeruginosa. Proc Natl Acad Sci U S A. 2002;99:7072-7077.

In the marine environment, exogenous siderophores affect the synthesis of induced siderophores and other iron acquisition mechanisms by others microbial species, working as signaling compounds that influence the growth of marine bacteria under iron-limited conditions. Many strains of marine bacteria were reported to produce siderophores and iron-regulated outer membrane proteins only in the presence of exogenous siderophores produced by other species, such as N,N′-bis (2,3-dihydroxybenzoyl)-O-serylserine from a Vibrio sp., even under very low iron concentrations.9797 Guan LL, Kanoh K, Kamino K. Effect of exogenous siderophores on iron uptake activity of marine bacteria under iron-limited conditions. Appl Environ Microbiol. 2001;67:1710-1717.

Symbiotic interaction

A remarkably complex inter-kingdom interaction is the symbiotic relationship between Burkholderia, a genus of bacteria, and Rhizopus, a genus of phytopathogen fungi that causes causing rice seedling blight. The endosymbiotic bacteria Burkholderia spp. is responsible for the production of the phytotoxin rhizoxin, the causal agent of rice seedling blight.9898 Partida-Martinez LP, Hertweck C. Pathogenic fungus harbours endosymbiotic bacteria for toxin production. Nature. 2005;437:884-888. It was reported that in the absence of the endosymbiont, Rhizopus is not capable of produce spores, indicating that the fungus is dependent on factors produced by the symbiont to complete its life cycle.9999 Partida-Martinez LP, Monajembashi S, Greulich KO, Hertweck C. Endosymbiont-dependent host reproduction maintains bacterial-fungal mutualism. Curr Biol. 2007;17:773-777. This complex symbiont-pathogen-plant interaction is still poorly understood regarding the metabolites and mechanisms involved in the communication and interaction. A study on exopolysaccharide (EPS), which usually plays key roles in interactions, produced by Burkholderia rhizoxinica described a previously unknown structure of EPS. However, the loss of EPS production did not affect the endosymbiotinc interaction with Rhizopus microsporus, as shown by a targeted knockout mutant experiment.100100 Uzum Z, Silipo A, Lackner G, De Felice A, Molinaro A, Hertweck C. Structure, genetics and function of an exopolysaccharide produced by a bacterium living within fungal hyphae. Chembiochem. 2015;16:387-392.Burkholderia gladioli produces enacyloxins (polyketides with potent antibiotic activity) in co-culture with R. microsporus. The fungus induces the growth of B. gladioli resulting in an increased production of bongkrekic acid, which inhibited the growth of the fungus.101101 Ross C, Opel V, Scherlach K, Hertweck C. Biosynthesis of antifungal and antibacterial polyketides by Burkholderia gladioli in coculture with Rhizopus microsporus. Mycoses. 2014;57:48-55.

Quorum sensing

Quorum sensing (QS) is the bacterial cell-cell communication. This process involves the production and detection of signaling molecules (called autoinducers) allowing bacterial communities to express genes collectively.102102 Hawver LA, Jung SA, Ng WL. Specificity and complexity in bacterial quorun-sensing systems. FEMS Microbiol Rev. 2016;40(5):738-752. QS systems are different in Gram-negatives and Gram-positives, the signaling molecules are called acyl-homoserine-lactones (AHLs) in proteobacteria or cis-11-methyl-2-dodecanoic acid (also called diffusible signal factor - DSF) mainly in Xanthomonas and Xylella, gram negatives and gamma-butyrolactones in Streptomyces and peptides in Gram positives.103103 Lazdunski AM, Ventre I, Sturgis JN. Regulatory circuits and communication in Gram-negative bacteria. Nat Rev Microbiol. 2004;2:581-592.,104104 Danhorn T, Fuqua C. Biofilm formation by plant-associated bacteria. Annu Rev Microbiol. 2007;61:401-422.

The first QS system described was in the 1980s in Vibrio fischeri (formerly known as Photobacterium fischeri) bacterium. In the sea, it is in a low population density and does not luminesce. Therefore, when it is in a symbiotic association with fishes and squids it luminesces. After the autoinducer molecule reaches a threshold luminescence genes are activated. This light matches the moonlight, making the squid invisible to the predators below.105105 Boettcher KJ, Ruby EG, McFallNgai MJ. Bioluminescence in the symbiotic squid Euprymna scolopes is controlled by a daily biological rhythm. J Comp Physiol A. 1996;179:65-73.,106106 Engebrecht J, Nealson K, Silverman M. Bacterial bioluminescence - isolation and genetic-analysis of functions from Vibrio Fischeri. Cell. 1983;32:773-781.

In Gram-negative bacteria, two proteins are involved in QS system: the transcriptional regulator R (or LuxR) and the autoinducer synthase I (or LuxI). In V. fischeri this system is called LuxR/LuxI. The signaling molecule or autoinducer (AHL) ligates to the transcriptional regulator LuxR, this ligation is very specific, used for interspecies communication.107107 Fuqua WC, Winans SC, Greenberg EP. Quorum sensing in bacteria - the Luxr-Luxi family of cell density-responsive transcriptional regulators. J Bacteriol. 1994;176:269-275.,108108 Schaefer AL, Hanzelka BL, Eberhard A, Greenberg EP. Quorum sensing in Vibrio fischeri: probing autoinducer-LuxR interactions with autoinducer analogs. J Bacteriol. 1996;178:2897-2901. Therefore, there are several reports of intraspecific communication as well.109109 Steidle A, Sigl K, Schuhegger R, et al. Visualization of N-acylhomoserine lactone-mediated cell-cell communication between bacteria colonizing the tomato rhizosphere. Appl Environ Microb. 2001;67:5761-5770. Some bacteria present more than one system, for example, Rhizobium leguminosarum with five R proteins,110110 Gonzalez JE, Marketon MM. Quorum sensing in nitrogen-fixing rhizobia. Microbiol Mol Biol Rev. 2003;67:574-592. used for different functions: nodulation efficiency, growth inhibition, nitrogen fixation and plasmid transfer.111111 Boyer M, Wisniewski-Dye F. Cell-cell signalling in bacteria: not simply a matter of quorum. Fems Microbiol Ecol. 2009;70:1-19.

Thereby, QS can have different roles: fluorescence emission (as reported above with Vibrio fischeri example), virulence, sporulation, competence, antibiotic production and biofilm formation,102102 Hawver LA, Jung SA, Ng WL. Specificity and complexity in bacterial quorun-sensing systems. FEMS Microbiol Rev. 2016;40(5):738-752. and can act during the interaction of different organism: bacteria-bacteria, fungal-bacteria, bacteria-host (animal or plant). It regulates a large number of genes, around 6-10% of the microbial genome.103103 Lazdunski AM, Ventre I, Sturgis JN. Regulatory circuits and communication in Gram-negative bacteria. Nat Rev Microbiol. 2004;2:581-592.

In gram-positive bacteria, specifically Bacillus subtilis and Streptococcus pneumoniae peptide signal can induce sporulation and competence development. This was evidenced by experiments showing that sporulation and competence are inefficient at low cell densities and needs a secreted bacterial factor.112112 Dunny GM, Leonard BAB. Cell-cell communication in gram-positive bacteria. Annu Rev Microbiol. 1997;51:527-564.

Concerning virulence, pathogens are able to control virulence factors expression by QS molecule. Vascular pathogen, such as Xanthomonas and Xylella uses DSF signaling to express virulence factor as well as biofilm formation104104 Danhorn T, Fuqua C. Biofilm formation by plant-associated bacteria. Annu Rev Microbiol. 2007;61:401-422.Xylella also uses DSF signaling to colonize the insect vector, which is key in the disease transmission.113113 Newman KL, Almeida RPP, Purcell AH, Lindow SE. Cell-cell signaling controls Xylella fastidiosa interactions with both insects and plants. Proc Natl Acad Sci U S A. 2004;101:1737-1742. Other vascular pathogen Pantoea stewartii uses AHL molecules to express disease, QS mutants of P. stewartii were not able to disperse and migrate in the vessels, consequently decreasing the disease.114114 Koutsoudis MD, Tsaltas D, Minogue TD, von Bodman SB. Quorum-sensing regulation governs bacterial adhesion, biofilm development, and host colonization in Pantoea stewartii subspecies stewartii. Proc Natl Acad Sci U S A. 2006;103:5983-5988. The epiphytic plant pathogen Pseudomonas syringae also uses AHL molecule in virulence. This bacterium is able to control motility and exopolysaccharide synthesis essential on biofilm formation and leave colonization.115115 Quinones B, Dulla G, Lindow SE. Quorum sensing regulates exopolysaccharide production, motility, and virulence in Pseudomonas syringae. Mol Plant Microbe Interact. 2005;18:682-693. Therefore, QS inhibitors (QSI) can reduce biofilm formation and increase de bacterial susceptibility to antibiotics. There are four strategies used to interfere with QS inhibition of: 1. signal generation; 2. signal dissemination, 3. Signal receptor and signaling response system.116116 Li YH, Tian X. Quorum sensing and bacterial social interactions in biofilms. Sensors (Basel). 2012;12:2519-2538.,117117 Abraham WR. Going beyond the control of quorum-sensing to combat biofilm infections. Antibiot Basel. 2016;5.

Reports of AHL degradation by environmental and clinic bacteria, affecting AHL signaling have been described. For example, P. aeruginosa and Burkholderia cepacia are associated to pneumoniae in cystic fibrosis patients and during this infection the cross talk seems to be an important strategy for both bacteria. P. aeruginosa produces AHL able to induce B. cepacia genes involved in biofilm formation.111111 Boyer M, Wisniewski-Dye F. Cell-cell signalling in bacteria: not simply a matter of quorum. Fems Microbiol Ecol. 2009;70:1-19. On the other hand, Non AHL producing bacteria can foreclose AHL movement, affecting AHL - mediated responses.118118 Mason VP, Markx GH, Thompson IP, Andrews JS, Manefield M. Colonial architecture in mixed species assemblages affects AHL mediated gene expression. FEMS Microbiol Lett. 2005;244:121-127. This cross-talking can occur between other organisms such as plants and bacteria, which is key during plant-bacteria interaction. Plants produce compounds that mimics AHL and interferes with AHL biosensors,119119 Teplitski M, Robinson JB, Bauer WD. Plants secrete substances that mimic bacterial N-acyl homoserine lactone signal activities and affect population density-dependent behaviors in associated bacteria. Mol Plant Microbe Interact. 2000;13:637-648. for example, Medicago sativa may produce a compound able to inhibit exopolysaccharides production in Sinorhizobium meliloti.120120 Keshavan ND, Chowdhary PK, Haines DC, Gonzalez JE. L-Canavanine made by Medicago sativa interferes with quorum sensing in Sinorhizobium meliloti. J Bacteriol. 2005;187:8427-8436. QS also regulates conjugative transfer during plant-Agrobacterium tumefaciens interaction, which bacteria induce crown-gall by transferring T-DNA, that codifies proteins involved in opine biosynthesis, to the plant. The conjugation is trigged by AHL molecules.111111 Boyer M, Wisniewski-Dye F. Cell-cell signalling in bacteria: not simply a matter of quorum. Fems Microbiol Ecol. 2009;70:1-19. This cross-talking can also occur bacteria-fungus and bacteria-animal. Fungus and animals can produce compounds that inhibit QS-controlled genes in P. aeruginosa.116116 Li YH, Tian X. Quorum sensing and bacterial social interactions in biofilms. Sensors (Basel). 2012;12:2519-2538.,121121 Rasmussen TB, Skindersoe ME, Bjarnsholt T, et al. Identity and effects of quorum-sensing inhibitors produced by Penicillium species. Microbiology. 2005;151:1325-1340.,122122 Park J, Kaufmann GF, Bowen JP, Arbiser JL, Janda KD, Solenopsin A. a venom alkaloid from the fire ant Solenopsis invicta, inhibits quorum-sensing signaling in Pseudomonas aeruginosa. J Infect Dis. 2008;198:1198-1201.

The Candida albicans and Pseudomonas aeruginosa interaction is an important model that show how fungi and bacteria can regulate each other by QS system. Farnesol (a sesquiterpene) and tyrosol's produced by Candida albicans are associated to control the physiology and virulence of this fungi. In fact, farnesol is associated to resistance to drugs, antimicrobial activity and inhibition of filamentation stage and biofilm formation, while tyrosol induces oxidative stress resistance, a shortened lag phase of growth and stimulate the germ tube in yeast cells and hyphae in the early stage of biofilm formation.123123 De Sordi L, Muhlschlegel FA. Quorum sensing and fungal-bacterial interactions in Candida albicans: a communicative network regulating microbial coexistence and virulence. FEMS Yeast Res. 2009;9:990-999. In the host, Candida albicans may share the same environment with the bacterium P. aeruginosa, which bacterium may present a complex QS system based on the synthesis of many molecules, such as 3-oxo-C12 homoserine-lactones (HSL) and 2-heptyl-3-hydroxy-4-quinolone (PQS-Pseudomonas quinolone signal). P. aeruginosa may attach on to a filamentous form of C. albicans and inhibit this fungus by synthesizing many molecules, including phenazines, pyocianyn, haemolytic phospholipase C,124124 Hogan DA, Kolter R. Pseudomonas-Candida interactions: an ecological role for virulence factors. Science. 2002;296:2229-2232. suggesting that these molecules are associated with niche construction during establishment in the host. During this interaction, the P. aeruginosa QS system may block the yeast-to-hypha transition or activates the hypha-to-yeast reversion, suggesting that C. albicans may sense the presence of the bacterium and activates a survival mechanism.123123 De Sordi L, Muhlschlegel FA. Quorum sensing and fungal-bacterial interactions in Candida albicans: a communicative network regulating microbial coexistence and virulence. FEMS Yeast Res. 2009;9:990-999. In another hand, the farnesol produced by C. albicans downregulate the PQS system of P. aeruginosa, inhibiting, in turn, the pyocyanin production.125125 Cugini C, Calfee MW, Farrow JM, Morales DK, Pesci EC, Hogan DA. Farnesol, a common sesquiterpene, inhibits PQS production in Pseudomonas aeruginosa. Mol Microbiol. 2007;65:896-906. This cross-talk between P. aeruginosa and C. albicans and based on the synthesis of farnesol, HSL and PQS allow the coexistence of these microbes in the same environment and control the population level of both, showing that this system may regulate the multi-trophic interaction in complex communities.

Concluding remarks

In the environment, microorganisms live in close contact with many different hosts and with each other in communities, usually including many species. In addition, they are also exposed to variation in the environmental conditions, which in turn affect the interaction among microorganisms and the host. The studies in microbial ecology, including the interaction among microbial species and between microorganism and the host has led to important findings in the ecology, human healthy and biotechnological researches, such as molecular mechanisms related to physiological response in human systemic diseases and antimicrobial drug development based on natural products, synthetic biology and quorum sensing.

Microbial interactions are highly complex and many mechanisms and molecules are involved, enabling that some microorganisms identify some species and respond to each other in a complex environment, including shifts in physical-chemical condition and presence of different hosts, many of them were presented in this review. However, there is still a lot to understand about the “molecular language” used by microorganisms and the molecules and signs related to interaction with the host. The development and adaptation of tools and methods including in vitro and in vivo models are still highly required to better understand and characterize the microbial interactions with more molecular details. In addition, understanding the connection between genomes, gene expression, and molecules in complex environments and communities comprise a very difficult challenge. The ways in which microbial species interact with each other and with the host are a complex issue that is only beginning to be understood, but recent studies have provided new insights in microbial interactions and their application in ecology and human healthy.

Acknowledgements

This work was supported by a grant from the Foundation for Research Assistance, São Paulo State, Brazil (Proc. 2012/24217-6 and 2015/11563-1). We thank FAPESP for M.N.D. (Proc. 2013/17314-08) and CNPq for R.M.B. (Proc. 141145/2012-9) fellowships. W.L.A. received Productivity-in-Research fellowship (Produtividade em Pesquisa - PQ) from the National Council for Scientific and Technological Development (CNPq).

REFERENCES

  • 1
    Frey-Klett P, Burlinson P, Deveau A, Barret M, Tarkka M, Sarniguet A. Bacterial-fungal interactions: hyphens between agricultural, clinical, environmental, and food microbiologists. Microbiol Mol Biol Rev 2011;75:583-609.
  • 2
    Faust K, Raes J. Microbial interactions: from networks to models. Nat Rev Microbiol 2012;10:538-550.
  • 3
    Phelan VV, Liu WT, Pogliano K, Dorrestein PC. Microbial metabolic exchange-the chemotype-to-phenotype link. Nat Chem Biol 2012;8:26-35.
  • 4
    Stuart LM, Paquette N, Boyer L. Effector-triggered versus pattern-triggered immunity: how animals sense pathogens. Nat Rev Immunol 2013;13:199-206.
  • 5
    Jimenez PN, Koch G, Thompson JA, Xavier KB, Cool RH, Quax WJ. The multiple signaling systems regulating virulence in Pseudomonas aeruginosa Microbiol Mol Biol Rev 2012;76:46-65.
  • 6
    Peters BM, Jabra-Rizk MA, O’May GA, Costerton JW, Shirtliff ME. Polymicrobial interactions: impact on pathogenesis and human disease. Clin Microbiol Rev 2012;25:193-213.
  • 7
    Brickman T, Armstrong S. Temporal signaling and differential expression of Bordetella iron transport systems: the role of ferrimones and positive regulators. Biometals 2009;22:33-41.
  • 8
    Peleg AY, Hogan DA, Mylonakis E. Medically important bacterial-fungal interactions. Nat Rev Microbiol 2010;8:340-349.
  • 9
    Clemente JC, Ursell LK, Parfrey LW, Knight R. The impact of the gut microbiota on human health: an integrative view. Cell 2012;148:1258-1270.
  • 10
    Knights D, Costello EK, Knight R. Supervised classification of human microbiota. FEMS Microbiol Rev 2011;35:343-359.
  • 11
    Virgin HW, Todd JA. Metagenomics and personalized medicine. Cell 2011;147:44-56.
  • 12
    Brakhage AA, Schroeckh V. Fungal secondary metabolites - strategies to activate silent gene clusters. Fungal Genet Biol 2011;48:15-22.
  • 13
    Oh DC, Kauffman CA, Jensen PR, Fenical W. Induced production of emericellamides A and B from the marine-derived fungus Emericella sp. in competing co-culture. J Nat Prod 2007;70:515-520.
  • 14
    Schroeckh V, Scherlach K, Nutzmann HW, et al. Intimate bacterial-fungal interaction triggers biosynthesis of archetypal polyketides in Aspergillus nidulans Proc Natl Acad Sci U S A 2009;106:14558-14563.
  • 15
    Marmann A, Aly AH, Lin W, Wang B, Proksch P. Co-cultivation - a powerful emerging tool for enhancing the chemical diversity of microorganisms. Mar Drugs 2014;12:1043-1065.
  • 16
    Netzker T, Fischer J, Weber J, et al. Microbial communication leading to the activation of silent fungal secondary metabolite gene clusters. Front Microbiol 2015;6:299.
  • 17
    Chamoun R, Aliferis KA, Jabaji S. Identification of signatory secondary metabolites during mycoparasitism of Rhizoctonia solani by Stachybotrys elegans Front Microbiol 2015;6:353.
  • 18
    van Elsas JD, Chiurazzi M, Mallon CA, Elhottova D, Kristufek V, Salles JF. Microbial diversity determines the invasion of soil by a bacterial pathogen. Proc Natl Acad Sci U S A 2012;109:1159-1164.
  • 19
    Song L, Wang Y, Tang W, Lei Y. Archaeal community diversity in municipal waste landfill sites. Appl Microbiol Biotechnol 2015;99:6125-6137.
  • 20
    Kent AD, Triplett EW. Microbial communities and their interactions in soil and rhizosphere ecosystems. Annu Rev Microbiol 2002;56:211-236.
  • 21
    Mikkelsen D, Kappler U, Webb RI, Rasch R, McEwan AG, Sly LI. Visualisation of pyrite leaching by selected thermophilic archaea: nature of microorganism-ore interactions during bioleaching. Hydrometallurgy 2007;88:143-153.
  • 22
    Scaria V, Hariharan M, Maiti S, Pillai B, Brahmachari SK. Host-virus interaction: a new role for microRNAs. Retrovirology 2006;3:68.
  • 23
    Zhou R, Rana TM. RNA-based mechanisms regulating host-virus interactions. Immunol Rev 2013;253:97-111.
  • 24
    Tarkka MT, Sarniguet A, Frey-Klett P. Inter-kingdom encounters: recent advances in molecular bacterium-fungus interactions. Curr Genet 2009;55:233-243.
  • 25
    Mendes R, Garbeva P, Raaijmakers JM. The rhizosphere microbiome: significance of plant beneficial, plant pathogenic, and human pathogenic microorganisms. FEMS Microbiol Rev 2013;37:634-663.
  • 26
    Hardoim PR, van Overbeek LS, Berg G, et al. The hidden world within plants: ecological and evolutionary considerations for defining functioning of microbial endophytes. Microbiol Mol Biol R 2015;79:293-320.
  • 27
    Hardoim PR, van Overbeek LS, Elsas JD. Properties of bacterial endophytes and their proposed role in plant growth. Trends Microbiol 2008;16:463-471.
  • 28
    Sun YL, Cheng ZY, Glick BR. The presence of a 1-aminocyclopropane-1-carboxylate (ACC) deaminase deletion mutation alters the physiology of the endophytic plant growth-promoting bacterium Burkholderia phytofirmans PsJN. Fems Microbiol Lett 2009;296:131-136.
  • 29
    Naveed M, Hussain MB, Zahir ZA, Mitter B, Sessitsch A. Drought stress amelioration in wheat through inoculation with Burkholderia phytofirmans strain PsJN. Plant Growth Regul 2014;73:121-131.
  • 30
    Dourado MN, Martins PF, Quecine MC, et al. Burkholderia sp. SCMS54 reduces cadmium toxicity and promotes growth in tomato. Ann Appl Biol 2013;163:494-507.
  • 31
    DiGiulio DB. Diversity of microbes in amniotic fluid. Semin Fetal Neonatal Med 2012;17:2-11.
  • 32
    DiGiulio DB, Romero R, Amogan HP, et al. Microbial prevalence, diversity and abundance in amniotic fluid during preterm labor: a molecular and culture-based investigation. PLoS ONE 2008;3:e3056.
  • 33
    Goldenberg RL, Culhane JF. Infection as a cause of preterm birth. Clin Perinatol 2003;30:677-700.
  • 34
    Arrieta MC, Stiemsma LT, Amenyogbe N, Brown EM, Finlay B. The intestinal microbiome in early life: health and disease. Front Immunol 2014;5:427.
  • 35
    McNally L, Brown SP. Building the microbiome in health and disease: niche construction and social conflict in bacteria. Philos Trans R Soc Lond B Biol Sci 2015;370.
  • 36
    Dobson A, Cotter PD, Ross RP, Hill C. Bacteriocin production: a probiotic trait? Appl Environ Microbiol 2012;78:1-6.
  • 37
    Kline KA, Falker S, Dahlberg S, Normark S, Henriques-Normark B. Bacterial adhesins in host-microbe interactions. Cell Host Microbe 2009;5:580-592.
  • 38
    Scher JU, Abramson SB. The microbiome and rheumatoid arthritis. Nat Rev Rheumatol 2011;7:569-578.
  • 39
    Wheeler R, Chevalier G, Eberl G, Gomperts Boneca I. The biology of bacterial peptidoglycans and their impact on host immunity and physiology. Cell Microbiol 2014;16:1014-1023.
  • 40
    Everson CA, Toth LA. Systemic bacterial invasion induced by sleep deprivation. Am J Physiol Regul Integr Comp Physiol 2000;278:R905-R916.
  • 41
    Krueger JM, Pappenheimer JR, Karnovsky ML. The composition of sleep-promoting factor isolated from human urine. J Biol Chem 1982;257:1664-1669.
  • 42
    Johannsen L, Toth LA, Rosenthal RS, et al. Somnogenic, pyrogenic, and hematologic effects of bacterial peptidoglycan. Am J Physiol 1990;258:R182-R186.
  • 43
    Berg G, Rybakova D, Grube M, Koberl M. The plant microbiome explored: implications for experimental botany. J Exp Bot 2016;67:995-1002.
  • 44
    Mendes R, Raaijmakers JM. Cross-kingdom similarities in microbiome functions. ISME J 2015;9:1905-1907.
  • 45
    Lakshmanan V, Selvaraj G, Bais HP. Functional soil microbiome: belowground solutions to an aboveground problem. Plant Physiol 2014;166:689-700.
  • 46
    Haldar S, Sengupta S. Plant-microbe cross-talk in the rhizosphere: insight and biotechnological potential. Open Microbiol J 2015;9:1-7.
  • 47
    Chaparro JM, Badri DV, Bakker MG, Sugiyama A, Manter DK, Vivanco JM. Root exudation of phytochemicals in Arabidopsis follows specific patterns that are developmentally programmed and correlate with soil microbial functions. PLoS ONE 2013;8:e55731.
  • 48
    Peters NK, Frost JW, Long SR. A plant flavone, luteolin, induces expression of rhizobium-meliloti nodulation genes. Science 1986;233:977-980.
  • 49
    Akiyama K, Matsuzaki K, Hayashi H. Plant sesquiterpenes induce hyphal branching in arbuscular mycorrhizal fungi. Nature 2005;435:824-827.
  • 50
    Reinhold-Hurek B, Bunger W, Burbano CS, Sabale M, Hurek T. Roots shaping their microbiome: global hotspots for microbial activity. Annu Rev Phytopathol 2015;53:403-424.
  • 51
    Ottesen AR, Pena AG, White JR, et al. Baseline survey of the anatomical microbial ecology of an important food plant: Solanum lycopersicum (tomato). BMC Microbiol 2013;:13.
  • 52
    Mendes R, Kruijt M, de Bruijn I, et al. Deciphering the rhizosphere microbiome for disease-suppressive bacteria. Science 2011;332:1097-1100.
  • 53
    Cordovez V, Carrion VJ, Etalo DW, et al. Diversity and functions of volatile organic compounds produced by Streptomyces from a disease-suppressive soil. Front Microbiol 2015;6:1081.
  • 54
    Ardanov P, Sessitsch A, Haggman H, Kozyrovska N, Pirttila AM. Methylobacterium-induced endophyte community changes correspond with protection of plants against pathogen attack. PLoS ONE 2012;7:e46802.
  • 55
    Mueller UG, Sachs JL. Engineering microbiomes to improve plant and animal health. Trends Microbiol 2015;23:606-617.
  • 56
    Berg G, Krause R, Mendes R. Cross-kingdom similarities in microbiome ecology and biocontrol of pathogens. Front Microbiol 2015;6:1311.
  • 57
    Keller NP, Turner G, Bennett JW. Fungal secondary metabolism - from biochemistry to genomics. Nat Rev Microbiol 2005;3:937-947.
  • 58
    Yin W, Keller NP. Transcriptional regulatory elements in fungal secondary metabolism. J Microbiol 2011;49:329-339.
  • 59
    Demain AL, Fang A. The natural functions of secondary metabolites. Adv Biochem Eng Biotechnol 2000;69:1-39.
  • 60
    Bilyk O, Luzhetskyy A. Metabolic engineering of natural product biosynthesis in actinobacteria. Curr Opin Biotechnol 2016;42:98-107.
  • 61
    Tata A, Perez C, Campos ML, Bayfield MA, Eberlin MN, Ifa DR. Imprint desorption electrospray ionization mass spectrometry imaging for monitoring secondary metabolites production during antagonistic interaction of fungi. Anal Chem 2015;87:12298-12304.
  • 62
    Johnstone TC, Nolan EM. Beyond iron: non-classical biological functions of bacterial siderophores. Dalton Trans 2015;44:6320-6339.
  • 63
    Schmerk CL, Welander PV, Hamad MA, et al. Elucidation of the Burkholderia cenocepacia hopanoid biosynthesis pathway uncovers functions for conserved proteins in hopanoid-producing bacteria. Environ Microbiol 2015;17:735-750.
  • 64
    Malott RJ, Steen-Kinnaird BR, Lee TD, Speert DP. Identification of hopanoid biosynthesis genes involved in polymyxin resistance in Burkholderia multivorans Antimicrob Agents Chemother 2012;56:464-471.
  • 65
    Lopez-Lara IM, Sohlenkamp C, Geiger O. Membrane lipids in plant-associated bacteria: their biosyntheses and possible functions. Mol Plant Microbe Interact 2003;16:567-579.
  • 66
    Prakash V. Endophytic fungi as resource of bioactive compounds. Int J Pharm Bio Sci 2015;6:887-898.
  • 67
    Suryanarayanan TS, Shaanker RU. Fungal endophytes - biology and bioprospecting preface. Curr Sci India 2015;109:37-38.
  • 68
    Schulz B, Boyle C. The endophytic continuum. Mycol Res 2005;109:661-686.
  • 69
    Strobel GA. Endophytes as sources of bioactive products. Microbes Infect 2003;5:535-544.
  • 70
    Abe N, Sugimoto O, Arakawa T, Tanji K, Hirota A. Sorbicillinol, a key intermediate of bisorbicillinoid biosynthesis in Trichoderma sp USF-2690. Biosci Biotechnol Biochem 2001;65:2271-2279.
  • 71
    Salas-Marina MA, Silva-Flores MA, Uresti-Rivera EE, Castro-Longoria E, Herrera-Estrella A, Casas-Flores S. Colonization of Arabidopsis roots by Trichoderma atroviride promotes growth and enhances systemic disease resistance through jasmonic acid/ethylene and salicylic acid pathways. Eur J Plant Pathol 2011;131:15-26.
  • 72
    Araujo WL, Marcon J, Maccheroni W, Van Elsas JD, Van Vuurde JW, Azevedo JL. Diversity of endophytic bacterial populations and their interaction with Xylella fastidiosa in citrus plants. Appl Environ Microbiol 2002;68:4906-4914.
  • 73
    Lacava PT, Araujo WL, Marcon J, Maccheroni W, Azevedo JL. Interaction between endophytic bacteria from citrus plants and the phytopathogenic bacteria Xylella fastidiosa, causal agent of citrus-variegated chlorosis. Lett Appl Microbiol 2004;39:55-59.
  • 74
    Dourado MN, Santos DS, Nunes LR, Costa de Oliveira RL, de Oliveira MV, Araujo WL. Differential gene expression in Xylella fastidiosa 9a5c during co-cultivation with the endophytic bacterium Methylobacterium mesophilicum SR1.6/6. J Basic Microbiol 2015;55:1357-1366.
  • 75
    Araujo WL, Creason AL, Mano ET, et al. Genome sequencing and transposon mutagenesis of Burkholderia seminalis TC3.4.2R3 identify genes contributing to suppression of orchid necrosis caused by B gladioli Mol Plant Microbe Interact 2016;29:435-446.
  • 76
    Kim HS, Schell MA, Yu Y, et al. Bacterial genome adaptation to niches: divergence of the potential virulence genes in three Burkholderia species of different survival strategies. BMC Genom 2005;6:174.
  • 77
    Sim BM, Chantratita N, Ooi WF, et al. Genomic acquisition of a capsular polysaccharide virulence cluster by non-pathogenic Burkholderia isolates. Genome Biol 2010;11:R89.
  • 78
    Bradley AS, Pearson A, Sáenz JP, Marx CJ. Adenosylhopane: the first intermediate in hopanoid side chain biosynthesis. Org Geochem 2010;41:1075-1081.
  • 79
    Welander PV, Hunter RC, Zhang L, Sessions AL, Summons RE, Newman DK. Hopanoids play a role in membrane integrity and pH homeostasis in Rhodopseudomonas palustris TIE-1. J Bacteriol 2009;191:6145-6156.
  • 80
    Seipke RF, Loria R. Hopanoids are not essential for growth of Streptomyces scabies 87-22. J Bacteriol 2009;191:5216-5223.
  • 81
    Jones DS, Albrecht HL, Dawson KS, et al. Community genomic analysis of an extremely acidophilic sulfur-oxidizing biofilm. ISME J 2012;6:158-170.
  • 82
    Muller EE, Hourcade E, Louhichi-Jelail Y, Hammann P, Vuilleumier S, Bringel F. Functional genomics of dichloromethane utilization in Methylobacterium extorquens DM4. Environ Microbiol 2011;13:2518-2535.
  • 83
    Saenz JP, Grosser D, Bradley AS, et al. Hopanoids as functional analogues of cholesterol in bacterial membranes. Proc Natl Acad Sci U S A 2015;112:11971-11976.
  • 84
    Schmerk CL, Bernards MA, Valvano MA. Hopanoid production is required for low-pH tolerance, antimicrobial resistance, and motility in Burkholderia cenocepacia J Bacteriol 2011;193:6712-6723.
  • 85
    Nalin R, Putra SR, Domenach AM, Rohmer M, Gourbiere F, Berry AM. High hopanoid/total lipids ratio in Frankia mycelia is not related to the nitrogen status. Microbiology 2000;146:3013-3019.
  • 86
    Kulkarni G, Busset N, Molinaro A, et al. Specific hopanoid classes differentially affect free-living and symbiotic states of Bradyrhizobium diazoefficiens MBio 2015;6:e01251-e01315.
  • 87
    Morissette DC, Driscoll BT, Jabaji-Hare S. Molecular cloning, characterization, and expression of a cDNA encoding an endochitinase gene from the mycoparasite Stachybotrys elegans Fungal Genet Biol 2003;39:276-285.
  • 88
    Morissette DC, Dauch A, Beech R, Masson L, Brousseau R, Jabaji-Hare S. Isolation of mycoparasitic-related transcripts by SSH during interaction of the mycoparasite Stachybotrys elegans with its host Rhizoctonia solani Curr Genet 2008;53:67-80.
  • 89
    Chamoun R, Jabaji S. Expression of genes of Rhizoctonia solani and the biocontrol Stachybotrys elegans during mycoparasitism of hyphae and sclerotia. Mycologia 2011;103:483-493.
  • 90
    Martins MB, Carvalho I. Diketopiperazines: biological activity and synthesis. Tetrahedron 2007;63:9923-9932.
  • 91
    McCormick SP, Stanley AM, Stover NA, Alexander NJ. Trichothecenes: from simple to complex mycotoxins. Toxins 2011;3:802-814.
  • 92
    Traxler MF, Watrous JD, Alexandrov T, Dorrestein PC, Kolter R. Interspecies interactions stimulate diversification of the Streptomyces coelicolor secreted metabolome. MBio 2013;4.
  • 93
    Nutzmann HW, Reyes-Dominguez Y, Scherlach K, et al. Bacteria-induced natural product formation in the fungus Aspergillus nidulans requires Saga/Ada-mediated histone acetylation. Proc Natl Acad Sci U S A 2011;108:14282-14287.
  • 94
    Faraldo-Gomez JD, Sansom MS. Acquisition of siderophores in gram-negative bacteria. Nat Rev Mol Cell Biol 2003;4:105-116.
  • 95
    Visca P, Imperi F, Lamont IL. Pyoverdine siderophores: from biogenesis to biosignificance. Trends Microbiol 2007;15:22-30.
  • 96
    Lamont IL, Beare PA, Ochsner U, Vasil AI, Vasil ML. Siderophore-mediated signaling regulates virulence factor production in Pseudomonas aeruginosa Proc Natl Acad Sci U S A 2002;99:7072-7077.
  • 97
    Guan LL, Kanoh K, Kamino K. Effect of exogenous siderophores on iron uptake activity of marine bacteria under iron-limited conditions. Appl Environ Microbiol 2001;67:1710-1717.
  • 98
    Partida-Martinez LP, Hertweck C. Pathogenic fungus harbours endosymbiotic bacteria for toxin production. Nature 2005;437:884-888.
  • 99
    Partida-Martinez LP, Monajembashi S, Greulich KO, Hertweck C. Endosymbiont-dependent host reproduction maintains bacterial-fungal mutualism. Curr Biol 2007;17:773-777.
  • 100
    Uzum Z, Silipo A, Lackner G, De Felice A, Molinaro A, Hertweck C. Structure, genetics and function of an exopolysaccharide produced by a bacterium living within fungal hyphae. Chembiochem 2015;16:387-392.
  • 101
    Ross C, Opel V, Scherlach K, Hertweck C. Biosynthesis of antifungal and antibacterial polyketides by Burkholderia gladioli in coculture with Rhizopus microsporus Mycoses 2014;57:48-55.
  • 102
    Hawver LA, Jung SA, Ng WL. Specificity and complexity in bacterial quorun-sensing systems. FEMS Microbiol Rev 2016;40(5):738-752.
  • 103
    Lazdunski AM, Ventre I, Sturgis JN. Regulatory circuits and communication in Gram-negative bacteria. Nat Rev Microbiol 2004;2:581-592.
  • 104
    Danhorn T, Fuqua C. Biofilm formation by plant-associated bacteria. Annu Rev Microbiol 2007;61:401-422.
  • 105
    Boettcher KJ, Ruby EG, McFallNgai MJ. Bioluminescence in the symbiotic squid Euprymna scolopes is controlled by a daily biological rhythm. J Comp Physiol A 1996;179:65-73.
  • 106
    Engebrecht J, Nealson K, Silverman M. Bacterial bioluminescence - isolation and genetic-analysis of functions from Vibrio Fischeri. Cell 1983;32:773-781.
  • 107
    Fuqua WC, Winans SC, Greenberg EP. Quorum sensing in bacteria - the Luxr-Luxi family of cell density-responsive transcriptional regulators. J Bacteriol 1994;176:269-275.
  • 108
    Schaefer AL, Hanzelka BL, Eberhard A, Greenberg EP. Quorum sensing in Vibrio fischeri: probing autoinducer-LuxR interactions with autoinducer analogs. J Bacteriol 1996;178:2897-2901.
  • 109
    Steidle A, Sigl K, Schuhegger R, et al. Visualization of N-acylhomoserine lactone-mediated cell-cell communication between bacteria colonizing the tomato rhizosphere. Appl Environ Microb 2001;67:5761-5770.
  • 110
    Gonzalez JE, Marketon MM. Quorum sensing in nitrogen-fixing rhizobia. Microbiol Mol Biol Rev 2003;67:574-592.
  • 111
    Boyer M, Wisniewski-Dye F. Cell-cell signalling in bacteria: not simply a matter of quorum. Fems Microbiol Ecol 2009;70:1-19.
  • 112
    Dunny GM, Leonard BAB. Cell-cell communication in gram-positive bacteria. Annu Rev Microbiol 1997;51:527-564.
  • 113
    Newman KL, Almeida RPP, Purcell AH, Lindow SE. Cell-cell signaling controls Xylella fastidiosa interactions with both insects and plants. Proc Natl Acad Sci U S A 2004;101:1737-1742.
  • 114
    Koutsoudis MD, Tsaltas D, Minogue TD, von Bodman SB. Quorum-sensing regulation governs bacterial adhesion, biofilm development, and host colonization in Pantoea stewartii subspecies stewartii. Proc Natl Acad Sci U S A 2006;103:5983-5988.
  • 115
    Quinones B, Dulla G, Lindow SE. Quorum sensing regulates exopolysaccharide production, motility, and virulence in Pseudomonas syringae Mol Plant Microbe Interact 2005;18:682-693.
  • 116
    Li YH, Tian X. Quorum sensing and bacterial social interactions in biofilms. Sensors (Basel) 2012;12:2519-2538.
  • 117
    Abraham WR. Going beyond the control of quorum-sensing to combat biofilm infections. Antibiot Basel 2016;5.
  • 118
    Mason VP, Markx GH, Thompson IP, Andrews JS, Manefield M. Colonial architecture in mixed species assemblages affects AHL mediated gene expression. FEMS Microbiol Lett 2005;244:121-127.
  • 119
    Teplitski M, Robinson JB, Bauer WD. Plants secrete substances that mimic bacterial N-acyl homoserine lactone signal activities and affect population density-dependent behaviors in associated bacteria. Mol Plant Microbe Interact 2000;13:637-648.
  • 120
    Keshavan ND, Chowdhary PK, Haines DC, Gonzalez JE. L-Canavanine made by Medicago sativa interferes with quorum sensing in Sinorhizobium meliloti J Bacteriol 2005;187:8427-8436.
  • 121
    Rasmussen TB, Skindersoe ME, Bjarnsholt T, et al. Identity and effects of quorum-sensing inhibitors produced by Penicillium species. Microbiology 2005;151:1325-1340.
  • 122
    Park J, Kaufmann GF, Bowen JP, Arbiser JL, Janda KD, Solenopsin A. a venom alkaloid from the fire ant Solenopsis invicta, inhibits quorum-sensing signaling in Pseudomonas aeruginosa J Infect Dis 2008;198:1198-1201.
  • 123
    De Sordi L, Muhlschlegel FA. Quorum sensing and fungal-bacterial interactions in Candida albicans: a communicative network regulating microbial coexistence and virulence. FEMS Yeast Res 2009;9:990-999.
  • 124
    Hogan DA, Kolter R. Pseudomonas-Candida interactions: an ecological role for virulence factors. Science 2002;296:2229-2232.
  • 125
    Cugini C, Calfee MW, Farrow JM, Morales DK, Pesci EC, Hogan DA. Farnesol, a common sesquiterpene, inhibits PQS production in Pseudomonas aeruginosa Mol Microbiol 2007;65:896-906.

Publication Dates

  • Publication in this collection
    Dec 2016

History

  • Received
    23 Sept 2016
  • Accepted
    07 Oct 2016
Sociedade Brasileira de Microbiologia USP - ICB III - Dep. de Microbiologia, Sociedade Brasileira de Microbiologia, Av. Prof. Lineu Prestes, 2415, Cidade Universitária, 05508-900 São Paulo, SP - Brasil, Ramal USP 7979, Tel. / Fax: (55 11) 3813-9647 ou 3037-7095 - São Paulo - SP - Brazil
E-mail: bjm@sbmicrobiologia.org.br