Genomic analysis of a Mycobacterium bovis bacillus [corrected] Calmette-Guérin strain isolated from an adult patient with pulmonary tuberculosis

For years, bacillus Calmette-Guérin (BCG) has served as the unique vaccine against tuberculosis and has generally been regarded as safe. However, a clinical strain labeled 3281 that was isolated from a TB patient was identified to be BCG. Via the combination of next-generation sequencing (NGS) and c...

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Bibliographic Details
Published in:PloS one 2015, Vol.10 (4), p.e0122403-e0122403
Main Authors: Li, Xuming, Chen, Liping, Zhu, Yongqiang, Yu, Xia, Cao, Jun, Wang, Rui, Lv, Xinyan, He, Jin, Guo, Aizhen, Huang, Hairong, Zheng, Huajun, Liu, Siguo
Format: Article
Language:English
Subjects:
Acids
Adult
Bacillus Calmette-Guerin vaccine
BCG
Drug resistance
Epitopes
Epitopes - chemistry
Gene sequencing
Genes
Genes, Bacterial
Genetic analysis
Genomic analysis
Genomics
High-Throughput Nucleotide Sequencing
Humans
Laboratories
Male
Molecular Sequence Data
Mycobacterium bovis
Mycobacterium bovis - genetics
Mycobacterium bovis - isolation & purification
Mycobacterium tuberculosis
Mycobacterium tuberculosis - genetics
Next-generation sequencing
Phylogeny
Sequence Analysis, DNA
Tuberculosis
Tuberculosis, Pulmonary - microbiology
Tuberculosis, Pulmonary - prevention & control
Vaccines
Virulence
Virulence - genetics
Virulence factors
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Summary:For years, bacillus Calmette-Guérin (BCG) has served as the unique vaccine against tuberculosis and has generally been regarded as safe. However, a clinical strain labeled 3281 that was isolated from a TB patient was identified to be BCG. Via the combination of next-generation sequencing (NGS) and comparative genomic analysis, unique 3281 genetic characteristics were revealed. A region containing the dnaA and dnaN genes that is closely related to the initial chromosome replication was found to repeat three times on the BCG Pasteur-specific tandem duplication region DU1. Due to the minimum number of epitopes in BCG strains, 3281 was inferred to have a high possibility for immune evasion. Additionally, variations in the virulence genes and predictions for potential virulence factors were analyzed. Overall, we report a pathogen that has never previously been thought to be pathogenic and initial insights that are focused on the genetic characteristics of virulent BCG.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0122403