Heteroresistance to Colistin in Klebsiella pneumoniae Associated with Alterations in the PhoPQ Regulatory System
Heteroresistance to Colistin in Klebsiella pneumoniae Associated with Alterations in the PhoPQ Regulatory System
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DOI：
10.1128/aac.05055-14
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发表时间：
2015-05-01
影响因子：
4.9
通讯作者：
Poirel, Laurent
中科院分区：
文献类型：
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作者：
Jayol, Aurelie;Nordmann, Patrice;Poirel, Laurent
研究了一株多重耐药肺炎克雷伯菌分离株对粘菌素表现出异源耐药性。粘菌素耐药亚群在蛋白质PhoP中包含单个氨基酸变化（Asp 191 Tyr），这是PhoPQ双组分系统的一部分，该系统激活负责L-氨基阿拉伯糖合成和多粘菌素耐药的pmrHFIJKLM表达。与野生型phoP基因互补试验恢复了对粘菌素的完全敏感性。然后，对粘菌素敏感亚群的分析显示，与粘菌素抗性亚群中的phoP基因相比，phoP基因部分缺失（25 bp）。该缺失破坏了phoP的阅读框架，导致更长且无活性的蛋白质（255对223个氨基酸长）。这是第一个报告显示的突变（S）在多粘菌素耐药性的参与PhoP。此外，这也是首次阐明克雷伯氏菌产生黏菌素异源抗性的机制。肺炎。
A multidrug-resistant Klebsiella pneumoniae isolate exhibiting heteroresistance to colistin was investigated. The colistin-resistant subpopulation harbored a single amino acid change (Asp191Tyr) in protein PhoP, which is part of the PhoPQ two-component system that activates pmrHFIJKLM expression responsible for L-aminoarabinose synthesis and polymyxin resistance. Complementation assays with a wild-type phoP gene restored full susceptibility to colistin. Then, analysis of the colistin-susceptible subpopulation showed a partial deletion (25 bp) in the phoP gene compared to that in the colistin-resistant subpopulation. That deletion disrupted the reading frame of phoP, leading to a longer and inactive protein (255 versus 223 amino acids long). This is the first report showing the involvement of mutation(s) in PhoP in colistin resistance. Furthermore, this is the first study to decipher the mechanisms leading to colistin heteroresistance in K. pneumoniae.