Zhao Shulong, Liang Xinyi, Li Huihui, Sun Jingfang, Jiang Fei, Kang Haiquan
Department of Laboratory Medicine, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221002, People's Republic of China.
School of Medical Technology, Xuzhou Medical University, Xuzhou, 221004, People's Republic of China.
Infect Drug Resist. 2025 Aug 12;18:4007-4022. doi: 10.2147/IDR.S526613. eCollection 2025.
Carbapenem-resistant Enterobacterales (CRE) infections pose a significant global public health threat, with colistin as the last line of defense. Increasing colistin resistance presents a formidable clinical challenge. This study aimed to elucidate the molecular characteristics and resistance mechanisms of clinical colistin-resistant (ColR) CRE strains in Xuzhou, China.
The broth microdilution method and PCR were performed to detect antibiotic resistance phenotype and resistance genotype. Pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) were used to determine genetic relatedness. Whole-genome sequencing (WGS) was carried out to characterize plasmids carrying resistance genes. Phylogenetic analysis was conducted by constructing phylogenetic tree based on single nucleotide polymorphism (SNP) and core genome multilocus sequence typing (cgMLST).
In 14 ColR-carbapenem-resistant (ColR-CRKP) strains, the inactivation of the gene leads to colistin resistance. The gene, carried by a plasmid, mediated colistin resistance in 4 ColR-carbapenem-resistant (ColR-CREC) strains. PFGE revealed potential cloning epidemics in both ColR-CRKP and ColR-CREC. WGS of demonstrated the distribution of multiple crucial resistance genes on four plasmids. Notably, was located on the IncI2 plasmid while was located on the IncFII plasmid. Phylogenetic trees, based on SNP and cgMLST, illustrate that the clonal epidemic strains, as exemplified by 104, have the potential to spread across regions and species.
This study underscores that mutations in the gene and the presence of contribute to the development of colistin resistance in CRE. Additionally, it enriches local epidemiological knowledge, facilitating a better understanding and control of the spread of .
耐碳青霉烯类肠杆菌科细菌（CRE）感染对全球公共卫生构成重大威胁，黏菌素是最后一道防线。黏菌素耐药性不断增加带来了严峻的临床挑战。本研究旨在阐明中国徐州临床耐黏菌素（ColR）CRE菌株的分子特征及耐药机制。
采用肉汤微量稀释法和PCR检测抗生素耐药表型和耐药基因型。使用脉冲场凝胶电泳（PFGE）和多位点序列分型（MLST）确定遗传相关性。进行全基因组测序（WGS）以鉴定携带耐药基因的质粒特征。通过基于单核苷酸多态性（SNP）和核心基因组多位点序列分型（cgMLST）构建系统发育树进行系统发育分析。
在14株耐碳青霉烯类的耐黏菌素（ColR-CRKP）菌株中， 基因的失活导致黏菌素耐药。由质粒携带的 基因介导了4株耐碳青霉烯类的耐黏菌素（ColR-CREC）菌株的黏菌素耐药性。PFGE显示ColR-CRKP和ColR-CREC中均存在潜在的克隆流行情况。 菌株的WGS显示四个质粒上存在多个关键耐药基因。值得注意的是， 位于IncI2质粒上，而 位于IncFII质粒上。基于SNP和cgMLST的系统发育树表明，以 104为例的克隆流行菌株有可能跨区域和跨物种传播。
本研究强调 基因的突变和 的存在促成了CRE中黏菌素耐药性的产生。此外，它丰富了当地的流行病学知识，有助于更好地理解和控制 的传播。
