Transcriptomic analysis of induced resistance to polymyxin in carbapenem-resistant Enterobacter cloacae complex isolate carrying mcr-9

作者：Jiming Wu, L. Liu, Jianmin Wang, Ying Wang, Xinhui Li, Xiaoyu Wang, Shan Jiang, Wengang Li, Jisheng Zhang, Xiaoli Zhang · 发表于：Journal of Global Antimicrobial Resistance · 年份：2024 · DOI：10.1016/j.jgar.2024.04.006 · 被引用次数：5 · 研究领域：Antibiotic Resistance in Bacteria、Bacterial Genetics and Biotechnology、Microbial Natural Products and Biosynthesis

OBJECTIVES: Polymyxins are currently the last-resort treatment against multi-drug resistant Gram-negative bacterial infections, but plasmid-mediated mobile polymyxin resistance genes (mcr) threaten its efficacy, especially in carbapenem-resistant Enterobacter cloacae complex (CRECC). The objective of this study was to provide insights into the mechanism of polymyxin-induced bacterial resistance and the effect of overexpression of mcr-9. METHODS: The clinical strain CRECC414 carrying the mcr-9 gene was treated with a gradient concentration of polymyxin. Subsequently, the broth microdilution was used to determine the minimum inhibitory concentration (MIC) and RT-qPCR was utilized to assess mcr-9 expression. Transcriptome sequencing and whole genome sequencing (WGS) was utilized to identify alterations in strains resulting from increased polymyxin resistance, and significant transcriptomic differences were analysed alongside a comprehensive examination of metabolic networks at the genomic level. RESULTS: Polymyxin treatment induced the upregulation of mcr-9 expression and significantly elevated the MIC of the strain. Furthermore, the WGS and transcriptomic results revealed a remarkable up-regulation of arnBCADTEF gene cassette, indicating that the Arn/PhoPQ system-mediated L-Ara4N modification is the preferred mechanism for achieving high levels of resistance. Additionally, significant alterations in bacterial gene expression were observed with regards to multidrug efflux pumps,...