文献类型：期刊文献

中文题名：fosA6亚型突变与耐碳青霉烯类肺炎克雷伯菌磷霉素耐药及表型异质性

英文题名：Mutation of fosA6 subtype and fosfomycin resistance and phenotypic heterogeneity in carbapenem-resistant Klebsiella pneumoniae

作者：郭超[1];张晓芳[2];何天鹏[2];王东亮[2];何锦[2];袁媛[3]

第一作者：郭超

机构：[1]甘肃中医药大学第一临床医学院,甘肃兰州730000;[2]甘肃省人民医院重症医学科,甘肃兰州730000;[3]上海中医药大学附属龙华医院重症医学科,上海徐汇200030

第一机构：甘肃中医药大学临床医学院

年份：2026

卷号：36

期号：8

起止页码：1198

中文期刊名：中华医院感染学杂志

外文期刊名：Chinese Journal of Nosocomiology

收录：;北大核心:【北大核心2023】；

基金：甘肃省卫生健康行业科研计划(GSWSKY2020-37);甘肃省人民医院院内基金项目(20GSSY2-6)。

语种：中文

中文关键词：耐碳青霉烯类肺炎克雷伯菌;磷霉素耐药;fosA6基因;亚型突变;最低抑菌浓度

外文关键词：Carbapenem-resistant Klebsiella pneumoniae;Fosfomycin resistance;fosA6 gene;Subtype mutation;Minimum inhibitory concentration

摘要：目的探究耐碳青霉烯类肺炎克雷伯菌(CRKP)多重耐药机制,磷霉素作为替代治疗药,分析fosA6基因及其突变与磷霉素耐药、表型异质性的关联。方法收集37株CRKP,采用E-test法测定磷霉素对菌株的最低抑菌浓度(MIC);通过二代测序技术分析fosA6基因的携带与突变情况,并统计其与MIC值的相关性。结果在37株CRKP中,所有菌株均携带fosA6基因。其中,6株鉴定出fosA6基因亚型突变(包括V57I、P60S、V91I等)。表型分析显示,携带这些突变菌株的磷霉素MIC值(≤32μg/ml)显著低于未突变菌株。fosA6基因亚型突变与磷霉素MIC值的降低之间存在显著相关性(P<0.05)。结论fosA6是CRKP磷霉素耐药的核心基因,其特定亚型突变(V57I、P60S、V91I)可显著削弱酶活性,导致耐药水平下降,揭示了“功能减损性突变”在耐药异质性中的关键作用,为临床用药与耐药监测提供了新视角。
OBJECTIVE To explore the multidrug resistance mechanisms of carbapenem-resistant Klebsiella pneumoniae(CRKP),and analyze the association between the fosA6 gene and its mutations with fosfomycin resistance and phenotypic heterogeneity,with fosfomycin as an alternative therapeutic agent.METHODS A total of 37 strains of CRKP were collected.The minimum inhibitory concentration(MIC)of fosfomycin against the strains was determined through the E-test method.The carriage and mutations of the fosA6 gene were analyzed through next-generation sequencing technology,and its correlation with MIC values was statistically analyzed.RESULTS Among the 37 CRKP strains in the whole study,all carried the fosA6 gene.Among them,mutations in the fosA6 gene subtype were identified in 6 strains(including V57I,P60S,V91I,etc.).Phenotypic analysis showed that the fosfomycin MIC values(≤32μg/ml)of strains carrying these mutations were significantly lower than those of non-mutated strains.There was a significant correlation between mutations in the fosA6 gene subtype and a decrease in fosfomycin MIC values(P<0.05).CONCLUSIONS The fosA6 gene is a core gene responsible for fosfomycin resistance in CRKP.Specific subtype mutations(V57I,P60S,V91I)can significantly weaken enzyme activity,leading to a decrease in drug resistance levels.This reveals the crucial role of"loss-of-function mutations"in resistance heterogeneity and provides a new perspective for clinical medication and resistance monitoring.