MRC Centre for Molecular Bacteriology and Infection, Department of Life Sciences, Faculty of Natural Sciences, Imperial College London, London, SW7 2AZ, UK.
Department of Bacteriology- Hygiene, Bicêtre Hospital, Assistance Publique - Hôpitaux de Paris, Le Kremlin-Bicêtre, France.
Sci Rep. 2018 Nov 15;8(1):16910. doi: 10.1038/s41598-018-35041-y.
With the dissemination of extremely drug resistant bacteria, colistin is now considered as the last-resort therapy for the treatment of infection caused by Gram-negative bacilli (including carbapenemase producers). Unfortunately, the increase use of colistin has resulted in the emergence of resistance as well. In A. baumannii, colistin resistance is mostly caused by the addition of phosphoethanolamine to the lipid A through the action of a phosphoethanolamine transferase chromosomally-encoded by the pmrC gene, which is regulated by the two-component system PmrA/PmrB. In A. baumannii clinical isolate the main resistance mechanism to colistin involves mutations in pmrA, pmrB or pmrC genes leading to the overexpression of pmrC. Although, rapid detection of resistance is one of the key issues to improve the treatment of infected patient, detection of colistin resistance in A. baumannii still relies on MIC determination through microdilution, which is time-consuming (16-24 h). Here, we evaluated the performance of a recently described MALDI-TOF-based assay, the MALDIxin test, which allows the rapid detection of colistin resistance-related modifications to lipid A (i.e phosphoethanolamine addition). This test accurately detected all colistin-resistant A. baumannii isolates in less than 15 minutes, directly on intact bacteria with a very limited sample preparation prior MALDI-TOF analysis.
随着超级耐药菌的传播，黏菌素现在被认为是治疗革兰氏阴性杆菌（包括碳青霉烯酶产生菌）感染的最后手段。不幸的是，黏菌素的大量使用也导致了耐药性的出现。在鲍曼不动杆菌中，黏菌素耐药性主要是通过磷酸乙醇胺转移酶的作用，将磷酸乙醇胺添加到脂 A 上而产生的，该酶由 pmrC 基因编码，受 PmrA/PmrB 二组分系统调控。在鲍曼不动杆菌临床分离株中，对黏菌素的主要耐药机制涉及 pmrA、pmrB 或 pmrC 基因的突变，导致 pmrC 的过度表达。虽然快速检测耐药性是改善感染患者治疗的关键问题之一，但鲍曼不动杆菌中黏菌素耐药性的检测仍然依赖于通过微量稀释法进行 MIC 测定，这很耗时（16-24 小时）。在这里，我们评估了一种最近描述的 MALDI-TOF 基于检测方法 MALDIxin 测试的性能，该方法允许快速检测脂 A 上与黏菌素耐药相关的修饰（即磷酸乙醇胺的添加）。该测试在不到 15 分钟的时间内准确地检测到所有黏菌素耐药的鲍曼不动杆菌分离株，直接对完整的细菌进行检测，在进行 MALDI-TOF 分析之前，只需进行非常有限的样本制备。
