Si Zaifeng, Zhao Shengmei, Hao Yingying, Wang Qian, Zhong Yanfa, Liu Yue, Chen Ran, Jin Yan, Lu Zhiming
Department of Clinical Laboratory, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People's Republic of China.
Department of Clinical Laboratory, Dezhou Municipal Hospital of Traditional Chinese Medicine, Dezhou, Shandong, People's Republic of China.
Infect Drug Resist. 2024 Aug 27;17:3723-3735. doi: 10.2147/IDR.S473580. eCollection 2024.
complex (ECC), which includes major nosocomial pathogens, causes urinary, respiratory, and bloodstream infections in humans, for which colistin is one of the last-line drugs.
This study aimed to analyse the epidemiology and resistance mechanisms of colistin-resistant complex (ECC) strains isolated from Shandong, China.
Two hundred non-repetitive ECC strains were collected from a tertiary hospital in Shandong Province, China, from June 2020 to June 2022. Whole-genome sequencing and bioinformatics analyses were performed to understand the molecular epidemiology of the colistin-resistant ECC strains. The nucleotide sequences of heat shock protein (hsp60) were analyzed by using BLAST search to classify ECC. The gene expression levels of , and were assessed using RT-qPCR. MALDI-TOF MS was used to analyse the modification of lipid A.
Twenty-three colistin-resistant strains were detected among the 200 ECC clinical strains (11.5%). The cluster analysis revealed that 20 of the 23 ECC strains belonged to heterogeneous resistance clusters. Variants of mgrB, phoPQ, and pmrAB, particularly phoQ and pmrB, were detected in the 23 ECC strains. The and genes were significantly overexpressed in all 23 colistin-resistant ECC strains (P < 0.05). Additionally, all 23 ECC strains contained modified lipid A related to colistin resistance, which showed five ion peaks at m/z 1876, 1920, 1955, 2114, and 2158. Among the 23 ECC strains, 6 strains possessed a phosphoethanolamine (pETN) moiety, 16 strains possessed a 4-amino-4-deoxy-L-arabinose (-L-Ara4N) moiety, and one strain had both pETN and -L-Ara4N moieties.
This study suggests that diverse colistin resistance existed in ECC, including unknown resistance mechanisms, exist in ECC. Mechanistic investigations of colistin resistance are warranted to optimise colistin use in clinical settings and minimise the emergence of resistance.
复杂肠杆菌科细菌（ECC）包括主要的医院病原体，可引起人类泌尿系统、呼吸系统和血流感染，而黏菌素是治疗这些感染的最后一线药物之一。
本研究旨在分析从中国山东分离出的耐黏菌素复杂肠杆菌科细菌（ECC）菌株的流行病学和耐药机制。
2020年6月至2022年6月期间，从中国山东省一家三级医院收集了200株非重复性ECC菌株。进行全基因组测序和生物信息学分析，以了解耐黏菌素ECC菌株的分子流行病学。使用BLAST搜索分析热休克蛋白（hsp60）的核苷酸序列，对ECC进行分类。使用RT-qPCR评估、和的基因表达水平。采用基质辅助激光解吸电离飞行时间质谱（MALDI-TOF MS）分析脂多糖A的修饰情况。
在200株ECC临床菌株中检测到23株耐黏菌素菌株（11.5%）。聚类分析显示，23株ECC菌株中有20株属于异质性耐药簇。在23株ECC菌株中检测到mgrB、phoPQ和pmrAB的变体，尤其是phoQ和pmrB。在所有23株耐黏菌素ECC菌株中，和基因均显著过表达（P < 0.05）。此外，所有23株ECC菌株均含有与耐黏菌素相关的修饰脂多糖A，在m/z 1876、1920、1955、2114和2158处显示出五个离子峰。在23株ECC菌株中，6株含有磷酸乙醇胺（pETN）基团，16株含有4-氨基-4-脱氧-L-阿拉伯糖（-L-Ara4N）基团，1株同时含有pETN和-L-Ara4N基团。
本研究表明，ECC中存在多种耐黏菌素机制，包括未知的耐药机制。有必要对耐黏菌素机制进行深入研究，以优化临床环境中黏菌素的使用，并尽量减少耐药性的出现。
