Pathways Regulating the pbgP Operon and Colistin Resistance in Klebsiella pneumoniae Strains
Pathways Regulating the pbgP Operon and Colistin Resistance in Klebsiella pneumoniae Strains
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DOI：
10.4014/jmb.1604.04016
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发表时间：
2016-09-01
影响因子：
2.8
通讯作者：
Ko, Kwan Soo
中科院分区：
文献类型：
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作者：
Choi, Myung-Jin;Kim, Sunju;Ko, Kwan Soo
在这项研究中，我们调查了粘菌素耐药机制与pbgP操纵子的调节肺炎克雷伯菌，使用4个等基因对粘菌素敏感菌株和他们的粘菌素耐药衍生物和2个粘菌素耐药的临床分离株。研究了PhoPQ、PmrAB和MgrB的氨基酸序列改变，并使用定量实时PCR测量了phoQ、pmrB、pmrD和pbgP的mRNA表达水平。phoQ和pmrB基因从两个粘菌素抗性衍生物134 R和063 R中缺失。我们发现phoQ、pmrD和pbgP在所有粘菌素耐药衍生物中均显著上调。然而，pmrB显着上调，只有两个粘菌素耐药衍生物和一个临床菌株。pmrB在其他菌株中没有过表达。粘菌素的最小抑制浓度在phoQ和pmrB缺失突变体中均显著降低，这些突变体来自过表达phoQ和pmrB的粘菌素抗性衍生物（134 R）。然而，粘菌素的敏感性恢复，只有在phoQ缺失的突变体从粘菌素耐药衍生物（063 R）没有过表达的pmrB。因此，pbgP操纵子的两种不同调节可能与粘菌素-大肠杆菌素拮抗剂K的形成有关。肺炎。
In this study, we investigated colistin resistance mechanisms associated with the regulation of the pbgP operon in Klebsiella pneumoniae, using four isogenic pairs of colistin-susceptible strains and their colistin-resistant derivatives and two colistin-resistant clinical isolates. Amino acid sequence alterations of PhoPQ, PmrAB, and MgrB were investigated, and mRNA expression levels of phoQ, pmrB, pmrD, and pbgP were measured using quantitative real-time PCR. The phoQ and pmrB genes were deleted from two colistin-resistant derivatives, 134R and 063R. We found that phoQ, pmrD, and pbgP were significantly upregulated in all colistin-resistant derivatives. However, pmrB was significantly upregulated in only two colistinresistant derivatives and one clinical strain. pmrB was not overexpressed in the other strains. The minimum inhibitory concentration of colistin was drastically lower in both phoQ-and pmrB-deleted mutants from a colistin-resistant derivative (134R) that was overexpressing phoQ and pmrB. However, colistin susceptibility was restored only in a phoQ-deleted mutant from a colistin-resistant derivative (063R) without overexpression of pmrB. In conclusion, two different regulations of the pbgP operon may associate with the development of colistin-resisant K. pneumoniae.