Genomic and proteomic analyses of Mycobacterium bovis BCG Mexico 1931 reveal a diverse immunogenic repertoire against tuberculosis infection

Orduña, Patricia; Cevallos, Miguel A.; León, Samuel Ponce de; Arvizu, Adriana; Hernández-González, Ismael; Mendoza‐Hernández, Guillermo; López-Vidal, Yolanda

doi:10.1186/1471-2164-12-493

Cited by 29 publications

(24 citation statements)

References 44 publications

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“…In this study, we also identified 25 RDs (11 previously published [3], [18], [22], [25], [26], [27], [28] and 14 new; Table S4) that cover one or more absence genes in the genome sequences of these BCG strains. The topological structure tree based on RDs (Figure 2b) more clearly shows the relationship among the M. bovis BCG and M. tuberculosis strains than does the NJ phylogenetic tree (Figure 2a).…”

Section: Resultsmentioning

confidence: 95%

“…Whole genome sequences of M. bovis (AF2122/97), seven strains of M. bovis BCG (BCG Mexico, BCG China, BCG Russia, BCG Tice, BCG Danish, Tokyo 172 and Pasteur) and five strains of M. tuberculosis (H37Rv, H37Ra, F11, KZN1435 and CDC1551) were downloaded from the NCBI database [3], [10], [11], [12], [13], [14], [15], [16], [17], [18]. Detailed information about these strains is listed in Table S2.…”

Section: Methodsmentioning

confidence: 99%

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Genome Sequencing and Analysis of BCG Vaccine Strains

Zhang

Zheng

et al. 2013

PLoS ONE

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BackgroundAlthough the Bacillus Calmette-Guérin (BCG) vaccine against tuberculosis (TB) has been available for more than 75 years, one third of the world's population is still infected with Mycobacterium tuberculosis and approximately 2 million people die of TB every year. To reduce this immense TB burden, a clearer understanding of the functional genes underlying the action of BCG and the development of new vaccines are urgently needed.Methods and FindingsComparative genomic analysis of 19 M. tuberculosis complex strains showed that BCG strains underwent repeated human manipulation, had higher region of deletion rates than those of natural M. tuberculosis strains, and lost several essential components such as T-cell epitopes. A total of 188 BCG strain T-cell epitopes were lost to various degrees. The non-virulent BCG Tokyo strain, which has the largest number of T-cell epitopes (359), lost 124. Here we propose that BCG strain protection variability results from different epitopes. This study is the first to present BCG as a model organism for genetics research. BCG strains have a very well-documented history and now detailed genome information. Genome comparison revealed the selection process of BCG strains under human manipulation (1908–1966).ConclusionsOur results revealed the cause of BCG vaccine strain protection variability at the genome level and supported the hypothesis that the restoration of lost BCG Tokyo epitopes is a useful future vaccine development strategy. Furthermore, these detailed BCG vaccine genome investigation results will be useful in microbial genetics, microbial engineering and other research fields.

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Section: Resultsmentioning

confidence: 95%

Section: Methodsmentioning

confidence: 99%

Genome Sequencing and Analysis of BCG Vaccine Strains

Zhang

Zheng

et al. 2013

PLoS ONE

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“…Interestingly, sequencing of BCG Mexico 1931 repositioned this strain from the DU2-III group into the DU2-IV group that includes BCG Pasteur, BCG Connaught, BCG Tice, BCG Frappier, and BCG Phipps. This analysis revealed that BCG Mexico was not originally derived from BCG Danish, as previously thought, and that this inconsistency was likely attributed to different BCG manufacturing periods in Mexico (69). Additionally, this project uncovered novel deletions in BCG Mexico that shed light on its evolution.…”

Section: Molecular Evolution and The Propagation Of Bcg Substrainsmentioning

confidence: 52%

BCG Vaccines

Tran

Liu

Behr³

2014

Microbiol Spectr

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BCG is the collective name for a family of live attenuated strains of Mycobacterium bovis that are currently used as the only vaccine against tuberculosis (TB). There are two major reasons for studying the genome of these organisms: (i) Because they are attenuated, BCG vaccines provide a window into Mycobacterium tuberculosis virulence, and (ii) because they have provided protection in several clinical trials and case-control studies, BCG vaccines may shed light on properties required of a TB vaccine. Since the determination of the M. tuberculosis genome in 1998, the study of BCG vaccines has accelerated dramatically, offering data on the genomic differences between virulent M. tuberculosis, M. bovis, and the vaccine strains. While these findings have been rewarding for the study of virulence, there is unfortunately less accrued knowledge about protection. In this chapter, we review briefly the history of BCG vaccines and then touch upon studies over the past two decades that help explain how BCG underwent attenuation, concluding with some more speculative comments as to how these vaccines might offer protection against TB.

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“…The sequences of these strains such as Tokyo 172 (NC_012207.1) and Moreau RDJ (NZ_AM412059.1) were generated from the small-insert libraries (1-4 kb) by using BigDye terminator chemistry on ABI377-or ABI3700-automated DNA sequencers [9][10][11][12]. The large-insert library (40 bp) preparation method was used for Mexico BCG sub-strain (NC_016804.1) sequencing [13]. Orduña et al [13] were first who used for BCG genome analysis -the next generation sequencing (NGS) based on 454 technology and Sanger method.…”

Section: Bcg Genome Sequencingmentioning

confidence: 99%

Mosaic Structure as the Main Feature of Mycobacterium bovis BCG Genomes

Lvovna¹,

Ivanovna²,

Sergeevna³

et al. 2018

Mycobacterium - Research and Development

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Background: The genome stability of attenuated live BCG vaccine preventing the acute forms of childhood tuberculosis is an important aspect of vaccine production. The purpose of our study was a whole genome comparative analysis of BCG sub-strains and identification of potential triggers of sub-strains' transition. Results: Genomes of three BCG Russia seed lots (1963, 1982, 2006 years) have been sequenced, and the stability of vaccine sub-strain genomes has been confirmed. A comparative genome analysis of nine Mycobacterium bovis BCG and three M. bovis strains revealed their specific genome features associated with prophage profiles. A number of prophage-coded homologs to Caudovirales ORFs were common to all BCG genomes. Prophage profiles of BCG Tice and BCG Montreal genomes were unique and coded homologs to herpes viruses ORFs. The data of phylogenetic analysis of BCG sub-strain groups based on whole genome sequences and genome restriction maps were in congruence with prophage profiles. The only fragmentary similarity of specific prophage sequences of BCG Tice, BCG Montreal, and BCG Russia 368 in pair-wise alignments was observed, suggesting the impact of prophages on mosaic structure of genomes. Conclusions: The whole genome sequencing approach is essential for genomes with mosaic structure, harboring numerous prophage sequences. Tools for prophage search are effective instruments in this analysis.

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Genomic and proteomic analyses of Mycobacterium bovis BCG Mexico 1931 reveal a diverse immunogenic repertoire against tuberculosis infection

Cited by 29 publications

References 44 publications

Genome Sequencing and Analysis of BCG Vaccine Strains

Genome Sequencing and Analysis of BCG Vaccine Strains

BCG Vaccines

Mosaic Structure as the Main Feature of Mycobacterium bovis BCG Genomes

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