Comparative Study of the Susceptibility to Oxidative Stress between Two Types of Mycobacterium bovis BCG Tokyo 172

Keiichi Taniguchi, Daisuke Hayashi, Naomi Yasuda, Mao Nakayama, Kaori Yazawa, Shouta Ogawa, Yuji Miyatake, Saki Suda, Haruka Tomita, Miki Tokuda, Saotomo Itoh, Jun ichi Maeyama, Naoya Ohara, Saburo Yamamoto, Shigeaki Hida, Kikuo Onozaki, Takemasa Takii

Research output: Contribution to journalArticlepeer-review

Abstract

Genomic analysis revealed that the vaccine seed lot of Mycobacterium bovis bacillus Calmette-Guérin (BCG) Tokyo 172 contains two subclones (types I and II), but their phenotypic differences have not been elucidated. In this study, we compared the susceptibility of bacilli types I and II to oxidative stress in vitro and within host cells. Notably, the subclones displayed similar superoxide dismutase activity; however, foam height in the catalase test and lysate catalase/peroxidase activity were higher for type I bacilli than for type II bacilli. Additionally, type I bacilli were less susceptible to hydrogen peroxide (Hx2O2) than type II bacilli. After exposure to Hx2O2, antioxidative stress response genes katG, ahpC, sodA, and trxA were more strongly induced in type I bacilli than in type II bacilli. Further, we investigated cell survival in macrophages. Fewer type II bacilli were recovered than type I bacilli. However, in the presence of apocynin, a specific inhibitor of NADPH oxidase, type II recovery was greater than that of type I. The production of interleukin 1β (IL-1β), IL-12 p40, and tumor necrosis factor alpha (TNF-α) was higher in type I bacillus-infected macrophages than in type II bacillus-infected macrophages. The proportions of type I and type II bacilli in vaccine lots over 3 years (100 lots) were 97.6%±.5% and 2.4%±.5%, respectively. The study results illustrated that type I bacilli are more resistant to oxidative stress than type II bacilli. Overall, these findings provide important information in terms of the quality control and safety of BCG Tokyo 172 vaccine.

Original languageEnglish
Pages (from-to)1-11
Number of pages11
JournalmSphere
Volume6
Issue number2
DOIs
Publication statusPublished - Mar 2021

Keywords

  • BCG vaccine
  • Mycobacterium tuberculosis
  • NADPH oxidase
  • cytokine
  • redox

ASJC Scopus subject areas

  • Microbiology
  • Molecular Biology

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