Global survey of Klebsiella pneumoniae major porins from ertapenem non‐susceptible isolates lacking carbapenemases
Global survey of Klebsiella pneumoniae major porins from ertapenem non‐susceptible isolates lacking carbapenemases
复制标题
缺乏碳青霉烯酶的厄他培南非敏感分离株中肺炎克雷伯菌主要孔蛋白的全球调查
DOI：
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发表时间：
2018
影响因子：
3
通讯作者：
K. Kazmierczak
中科院分区：
文献类型：
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作者：
M. Wise;E. Horvath;K. Young;D. Sahm;K. Kazmierczak
目的。为了了解肺炎克雷伯菌破坏孔蛋白的多样性，对一组不含传统碳青霉烯类水解酶但对厄他培南不敏感的分离株进行了主要外膜蛋白OmpK35和OmpK36的检测。方法：研究方法。2008-2014年间，作为监测抗菌素耐药性趋势(SMART)监测项目研究的一部分，全球范围内的肺炎克雷伯菌分离株的特征是它们的内酰胺酶基因携带和潜在的通透性缺陷。对487株不携带碳青霉烯酶基因但对厄他培南不敏感的菌株进行了OmpK35和OmpK36基因的序列分析。对两个主要孔蛋白基因均无明显遗传损伤的菌株进一步进行外膜蛋白SDS-PAGE检测。结果。大多数分离株，83.0%(404/487)，在ompK35和ompK36基因中的一个或两个显示出明显的基因突变。在鄂他培南MIC值最高的样本(>；4 mg L−1)中，60.5%(115/190)的样本同时存在两种porin基因突变。对没有明显基因突变的菌株进行了SDS-PAGE检测，发现90.4%(75/83)的菌株与厄他培南敏感的对照菌株相比，至少有一种主要omp基因的表达缺失或发生了变化。结论。本研究表明肺炎克雷伯菌的孔蛋白缺乏是一种普遍现象，与ESBLS和/或AmpC酶相结合，可能是本研究中观察到的埃他培南MIC升高的原因。
Purpose. To understand the diversity of porin disruption in Klebsiella pneumoniae, the major outer membrane protein (OMP) porins, OmpK35 and OmpK36, were examined in a set of isolates that did not harbour traditional carbapenem‐hydrolysing enzymes, but nevertheless tested non‐susceptible to ertapenem. Methods. A world‐wide collection of Klebsiella pneumoniae isolates that were part of the Study for Monitoring Antimicrobial Resistance Trends (SMART) surveillance project over the years 2008‐2014 were characterised with regard to their &bgr;‐lactamase gene carriage and potential permeability defects. Four hundred and eighty‐seven isolates that did not carry carbapenemase genes, but were non‐susceptible to ertapenem, were investigated by sequence analysis of the genes encoding OmpK35 and OmpK36. Isolates without obvious genetic lesions in either major porin gene were further examined by outer membrane protein SDS‐PAGE. Results. The majority of isolates, 83.0 % (404/487), exhibited clear genetic disruption in either or both of the ompK35 and ompK36 genes. Among the proportion of the collection with the highest ertapenem MIC value (>4 mg l−1), 60.5 % (115/190) showed mutation in both porin genes. Isolates without obvious genetic mutations were examined by SDS‐PAGE, and 90.4 % (75/83) were found to lack or show altered expression of at least one of the major OMPs when compared to an ertapenem sensitive control strain. Conclusion. This study illustrates that porin deficiency in Klebsiella pneumoniae is a widespread phenomenon, and in combination with ESBLs and/or AmpC enzymes, likely accounts for the elevated ertapenem MICs observed in this study.
影响因子：
3
作者：
Landman, David;Bratu, Simona;Quale, John
通讯作者：
Quale, John