論文

査読有り 国際誌
2020年7月1日

Bacterial population kinetics in heteroresistant Mycobacterium tuberculosis harbouring rare resistance-conferring mutations in gyrA and rpoB imply an epistatic interaction of mutations in a pre-XDR-TB patient.

The Journal of antimicrobial chemotherapy
  • Shiomi Yoshida
  • ,
  • Tomotada Iwamoto
  • ,
  • Kentaro Arikawa
  • ,
  • Tsuyoshi Sekizuka
  • ,
  • Makoto Kuroda
  • ,
  • Yoshikazu Inoue
  • ,
  • Satoshi Mitarai
  • ,
  • Taisuke Tsuji
  • ,
  • Kazunari Tsuyuguchi
  • ,
  • Katsuhiro Suzuki

75
7
開始ページ
1722
終了ページ
1725
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1093/jac/dkaa109

OBJECTIVES: Bacterial population kinetics of strains harbouring drug resistance-conferring mutations within a patient often show cryptic resistance in clinical practice. We report a case that showed emergence and dominance of Mycobacterium tuberculosis with uncommon rpoB and gyrA mutations, followed by an rpoC compensatory mutation, during treatment. METHODS: A pre-XDR-TB patient showed heteroresistance to rifampicin and levofloxacin during treatment as a result of intermittent self-cessation. WGS was applied to investigate intra-host strain composition using five pairs of isolates from sputum samples. RESULTS: The subclone in this study possessed rare mutations conferring resistance to rifampicin (rpoB V170F) and levofloxacin (gyrA S91P) and it rapidly outcompeted other subclones during treatment that included levofloxacin but not rifampicin (<7 days). The high-probability compensatory mutation rpoC V483A also emerged and became dominant subsequent to the rpoB V170F mutation. CONCLUSIONS: To the best of our knowledge, this is the first case showing the emergence of such a rare variant that dominated the population within a patient during treatment of TB.

リンク情報
DOI
https://doi.org/10.1093/jac/dkaa109
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/32303065

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