4.7 Article

Metronidazole-resistant Clostridioides difficile: genomic and transcriptomic traits acquired under in-vitro metronidazole induction

出版社

ELSEVIER
DOI: 10.1016/j.ijantimicag.2022.106570

关键词

Clostridioides difficile; Metronidazole; Resistance; Sequence; Mechanism

资金

  1. Shanghai Science and Technol-ogy Committee [21ZR1410800]
  2. National Natu-ral Science Foundation of China [81973369]

向作者/读者索取更多资源

This study investigates the genomic and transcriptional changes associated with metronidazole resistance in Clostridioides difficile strains. The findings reveal an association between genomic variation and metronidazole resistance, and suggest that metronidazole resistance in C. difficile is influenced by factors such as metronidazole metabolism, cell wall thickness, and efflux pumps. These findings contribute to a better understanding of metronidazole resistance in C. difficile.
Decreased effectiveness of metronidazole for the treatment of Clostridioides difficile infection has been documented. One reason for this is that levels of metronidazole in the colon are generally low; therefore, a modest increase in the minimum inhibitory concentration of metronidazole for C. difficile may result in an insufficient therapeutic concentration. Due to the lack of efficient genetic manipulation tools for C. difficile strains, the resistance mechanism is largely unknown. In this study, a metronidazole-resistant strain (SH182IR) was acquired by in-vitro induction with metronidazole from a clinical metronidazoleheteroresistant strain (SH182), and the genomic and transcriptional changes were investigated through whole-genome sequencing and RNA-seq. The morphology of the two strains was studied by transmission electron microscopy, and the roles of drug efflux pumps in metronidazole resistance were determined by inhibition assay. Genomic analysis showed that the ferrous iron transporter feoB3 was truncated in SH182IR, indicating that feoB3 contributed to the metronidazole resistance of C. difficile. RNA-seq analysis showed that genes involved in peptidoglycan synthesis, efflux pumps and metronidazole reductive action were expressed differentially between the two strains. Further cell imaging confirmed that cell wall thickness was significantly greater in SH182IR. The efflux pump inhibitor test showed that addition of reserpine or cyanide 3-chlorophenylhydrazone reduced metronidazole resistance in SH182IR, thus proving the role of efflux pumps in metronidazole resistance. These results found an association between genomic variation and metronidazole resistance in C. difficile, and show that metronidazole resistance in C. difficile is multi-factorial, involving metronidazole metabolism, cell wall thickness and efflux pumps. These findings will help improve knowledge and understanding of metronidazole resistance of C. difficile.(c) 2022 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.7
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据