Differential Impact of the rpoB Mutant on Rifampin and Rifabutin Resistance Signatures of Mycobacterium tuberculosis Is Revealed Using a Whole-Genome Sequencing Assay

Ming Chih Yu, Ching Sheng Hung, Chun Kai Huang, Cheng Hui Wang, Yu Chih Liang, Jung Chun Lin

研究成果: 雜誌貢獻文章同行評審

摘要

Drug resistance in Mycobacterium tuberculosis (MTB) has long been a serious health issue worldwide. Most drug-resistant MTB isolates were identified due to treatment failure or in clinical examinations 3;6 months postinfection. In this study, we propose a whole-genome sequencing (WGS) pipeline via the Nanopore MinION platform to facilitate the efficacy of phenotypic identification of clinical isolates. We used the Nanopore MinION platform to perform WGS of clinical MTB isolates, including susceptible (n = 30) and rifampin- (RIF) or rifabutin (RFB)-resistant isolates (n = 20) according to results of a susceptibility test. Nonsynonymous variants within the rpoB gene associated with RIF resistance were identified using the WGS analytical pipeline. In total, 131 variants within the rpoB gene in RIF-resistant isolates were identified. The presence of the emergent Asp531Gly or His445Gln was first identified to be associated with the rifampin and rifabutin resistance signatures of clinical isolates. The results of the minimum inhibitory concentration (MIC) test further indicated that the Ser450Leu or the mutant within the rifampin resistance-determining region (RRDR)-associated rifabutin-resistant signature was diminished in the presence of novel mutants, including Phe669Val, Leu206Ile, or Met148Leu, identified in this study.
原文英語
期刊Microbiology spectrum
10
發行號4
DOIs
出版狀態已發佈 - 8月 2022

ASJC Scopus subject areas

  • 生理學
  • 生態學
  • 免疫學與微生物學 (全部)
  • 遺傳學
  • 微生物學(醫學)
  • 細胞生物學
  • 傳染性疾病

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