PLoS ONE (Jan 2015)

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

  • Xuming Li,
  • Liping Chen,
  • Yongqiang Zhu,
  • Xia Yu,
  • Jun Cao,
  • Rui Wang,
  • Xinyan Lv,
  • Jin He,
  • Aizhen Guo,
  • Hairong Huang,
  • Huajun Zheng,
  • Siguo Liu

DOI
https://doi.org/10.1371/journal.pone.0122403
Journal volume & issue
Vol. 10, no. 4
p. e0122403

Abstract

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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.