Lipid phenotype of two distinct subpopulations of Mycobacterium bovis bacillus calmette-guérin Tokyo 172 substrain

Takashi Naka, Shinji Maeda, Mamiko Niki, Naoya Ohara, Saburo Yamamoto, Ikuya Yano, Jun Ichi Maeyama, Hisashi Ogura, Kazuo Kobayashi, Nagatoshi Fujiwara

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18 Citations (Scopus)

Abstract

Bacillus Calmette-Guérin (BCG) Tokyo 172 is a predominant World Health Organization Reference Reagent for theBCGvaccine. Recently, the BCG Tokyo 172 substrain was reported to consist of two subpopulations with different colony morphologies, smooth and rough. Smooth colonies had a characteristic 22-bp deletion in Rv3405c of the region of difference (RD) 16 (type I), and rough colonies were complete in this region (type II). We hypothesized that the morphological difference is related to lipid phenotype and affects their antigenicity. We determined the lipid compositions and biosynthesis of types I and II. Scanning electron microscopy showed that type I was 1.5 times longer than type II. Phenolic glycolipid (PGL) and phthiocerol dimycocerosate (PDIM) were found only in type I. Although it has been reported that the RD16 is involved in the expression of PGL, type II did not possess PGL/PDIM. We examined the ppsA-E gene responsible for PGL/PDIM biosynthesis and found that the existence of PGL/PDIM in types I and II is caused by a ppsA gene mutation not regulated by the RD16. PGL suppressed the host recognition of total lipids via Toll-like receptor 2, and this suggests that PGL is antigenic and involved in host responses, acting as a cell wall component. This is the first report to show the difference between lipid phenotypes of types I and II. It is important to clarify the heterogeneity of BCG vaccine substrains to discuss and evaluate the quality, safety, and efficacy of the BCG vaccine.

Original languageEnglish
Pages (from-to)44153-44161
Number of pages9
JournalJournal of Biological Chemistry
Volume286
Issue number51
DOIs
Publication statusPublished - Dec 23 2011

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Naka, T., Maeda, S., Niki, M., Ohara, N., Yamamoto, S., Yano, I., Maeyama, J. I., Ogura, H., Kobayashi, K., & Fujiwara, N. (2011). Lipid phenotype of two distinct subpopulations of Mycobacterium bovis bacillus calmette-guérin Tokyo 172 substrain. Journal of Biological Chemistry, 286(51), 44153-44161. https://doi.org/10.1074/jbc.M111.310037