Newly sequenced genomes of four Bacillus Calmette Guerin vaccines

Bacillus Calmette Guerin (BCG) vaccines comprise a family of related strains. Whole genome sequencing has allowed the better characterisation of the differences between many of the BCG vaccines. As sequencing technologies improve, updating of publicly available sequence data becomes common practice. We hereby announce the draft genome of four commonly used BCG vaccines in Brazil, Argentina and Venezuela.

Key words:
mycobacteria; BCG; whole genome sequencing.

Authorship

Maria Carolina Sisco ⁺+ Corresponding author: carolinasisco@gmail.com

Universidade Federal do Rio de Janeiro, Instituto de Microbiologia Paulo de Góes, Departamento de Microbiologia Médica, Laboratório de Micobactérias, Rio de Janeiro, RJ, BrasilUniversidade Federal do Rio de JaneiroBrazilRio de Janeiro, RJ, BrazilUniversidade Federal do Rio de Janeiro, Instituto de Microbiologia Paulo de Góes, Departamento de Microbiologia Médica, Laboratório de Micobactérias, Rio de Janeiro, RJ, Brasil

Fundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório de Biologia Molecular Aplicada às Micobactérias, Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz-FiocruzBrazilRio de Janeiro, RJ, BrazilFundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório de Biologia Molecular Aplicada às Micobactérias, Rio de Janeiro, RJ, Brasil

http://orcid.org/0000-0002-1387-6701

Marlei Gomés Silva

Beatriz Lopez

Instituto Nacional de Enfermedades Infecciosas, Buenos Aires, ArgentinaInstituto Nacional de Enfermedades InfecciosasArgentinaBuenos Aires, ArgentinaInstituto Nacional de Enfermedades Infecciosas, Buenos Aires, Argentina

Claudia Arguelles

Instituto Nacional de Producción de Biológicos Carlos G Malbrán, Buenos Aires, ArgentinaInstituto Nacional de Producción de Biológicos Carlos G MalbránArgentinaBuenos Aires, ArgentinaInstituto Nacional de Producción de Biológicos Carlos G Malbrán, Buenos Aires, Argentina

Leila Mendonça-Lima

Fundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório de Genômica Funcional e Bioinformática, Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz-FiocruzBrazilRio de Janeiro, RJ, BrazilFundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório de Genômica Funcional e Bioinformática, Rio de Janeiro, RJ, Brasil

Jacobus H de Waard

Servicio Autónomo Instituto de Biomedicina Dr Jacinto Convit, Caracas, VenezuelaServicio Autónomo Instituto de Biomedicina Dr Jacinto ConvitVenezuelaCaracas, VenezuelaServicio Autónomo Instituto de Biomedicina Dr Jacinto Convit, Caracas, Venezuela

One Health Research Group, Universidad de Las Américas, Facultad de Ciencias de la Salud, Quito, EcuadorOne Health Research GroupEcuadorQuito, EcuadorOne Health Research Group, Universidad de Las Américas, Facultad de Ciencias de la Salud, Quito, Ecuador

Rafael Silva Duarte

Philip Noel Suffys

+ Corresponding author: carolinasisco@gmail.com

PNS and RSD conceived the study design and analyses; MCS performed the DNA extraction, conceived and performed the Bioinformatic analyses; MGS assisted in the culture and DNA extraction; BL, CA, LM and JDW provided the vaccines ampoule or DNA and revised the manuscript. The manuscript was elaborated by MCS, PNS and RSD.

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Tables

Tables (3)

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TABLE I
Assembly statistics for the four vaccine strains sequenced

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TABLE II
Non-synonymous single nucleotide polymorphisms (SNPs) found in Bacillus Calmette Guerin (BCG) Moreau when using assembly NZ_AM412059^* as a reference

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TABLE III
Non-synonymous single nucleotide polymorphisms (SNPs) found in Bacillus Calmette Guerin (BCG) Danish when using assembly NZ_CP039850^* as a reference

TABLE I Assembly statistics for the four vaccine strains sequenced

Number of contigs	Moreau RDJ	Pasteur 1173P2	Sofia SL222	Danish 1331
Number of contigs	82	93	102	108
Genome size (bp)	4288.245	4.192.545	4.201.889	4.202.807
Coverage	414X	107X	101X	94X
% GC	65.62	65.48	65.45	65.47
N50	197411	84414	70691	70718
CDS	4232	4205	4245	4227
tRNAs	47	47	47	47

bp: base-pairs; %GC: guanine-cytosine content; CDS: coding sequences; tRNA: transfer RNA.

TABLE II Non-synonymous single nucleotide polymorphisms (SNPs) found in Bacillus Calmette Guerin (BCG) Moreau when using assembly NZ_AM412059^* as a reference

Position	NZ_AM412059	BCG Moreau	AA change	Gene
404956	T	G	Glu713Asp	Iron-sulphur-binding reductase
555536	C	T	Gly164Glu	FIG00821074: hypothetical protein
555569	G	A	Pro153Leu	FIG00821074: hypothetical protein
570675	T	G	Lys91Asn	Aliphatic amidase AmiE
878380	G	T	Gly233Val	Protease II (EC 3.4.21.83)
1217552	T	G	His65Gln	PE family protein
1618404	A	G	Asp284Gly	Anaerobic dimethyl sulfoxide reductase chain A
1618472	A	C	Met307Leu	Anaerobic dimethyl sulfoxide reductase chain A
1618722	G	C	Arg390Pro	Anaerobic dimethyl sulfoxide reductase chain A
1618779	T	G	Val409Gly	Anaerobic dimethyl sulfoxide reductase chain A
1731072	G	A	Ala234Thr	Sorbitol-6-phosphate 2-dehydrogenase
1985896	C	G	Pro114Ala	L-gulono-1,4-lactone oxidase
2400116	A	G	Leu184Pro	Cell division protein FtsL / proline rich membrane protein
2651260	C	G	Ala266Gly	PE family protein
2701298	G	T	Pro413Thr	Ribonuclease E
2760281	T	C	Ser266Gly	GTP-binding protein Obg
2760610	G	C	Ala156Gly	GTP-binding protein Obg
2760682	T	C	Glu132Gly	GTP-binding protein Obg
3149570	C	G	Leu224Val	Coenzyme F420-dependent oxidoreductase
3273878	A	G	Val602Ala	ATP-dependent DNA helicase RecG
3365033	A	C	Trp93Gly	Transcriptional regulator, TetR family
3809510	C	G	Gly67Ala	FIG00820542: hypothetical protein
3879667	A	G	Asn344Asp	GTP-binding protein Obg
3881120	T	G	Ile828Ser	GTP-binding protein Obg
3881141	C	A	Thr835Asn	GTP-binding protein Obg
3891798	T	G	Asp162Ala	Long-chain fatty-acid-CoA ligase Mycobacterial subgroup FadD19
3963021	C	G	Val222Leu	Transcriptional regulator, LacI family
4172275	T	G	Met67Leu	Membrane proteins related to metalloendopeptidases

*: accession number for the assembly of BCG Moreau reported by Gomes et al.⁽⁶⁾ A: adenine; G: guanine; C: cytosine; T: thymine; Glu: glutamic acid; Asp: aspartic acid; Gly: glycine; Pro: proline; Leu: leucine; Lys: lysine; Asn: asparagine; Val: valine; His: histidine; Gln: glutamine; Met: methionine; Arg: arginine; Thr: threonine; Ser: serine; Ala: alanine; Trp: tryptophan; Ile: isoleucine.

TABLE III Non-synonymous single nucleotide polymorphisms (SNPs) found in Bacillus Calmette Guerin (BCG) Danish when using assembly NZ_CP039850^* as a reference

Position	NZ_CP039850	BCG Danish	AA change	Gene
593769	C	T	Gln323**	SDR family oxidoreductase
2076695	C	A	Ala142Ser	M56 family metallopeptidase
2500583	T	C	His260Arg	Sulfotransferase
3745609	G	T	Ser434Tyr	PPE family protein
3839864	T	G	Thr135Pro	IMP dehydrogenase

*: accession number for the sequencing of BCG Danish reported by Borgers et al.⁽⁷⁾; **: indicates a stop codon; A: adenine; G: guanine; C: cytosine; T: thymine; Gln: glutamine; Ala: alanine; Ser: serine; Thr: threonine; Pro: proline; Tyr: tyrosine.

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Newly sequenced genomes of four Bacillus Calmette Guerin vaccines

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[1] + Corresponding author: carolinasisco@gmail.com