首页|耐药性肺结核患者结核分枝杆菌基因突变特点及药敏特性分析

耐药性肺结核患者结核分枝杆菌基因突变特点及药敏特性分析

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目的 探究耐药性结核分枝杆菌的药敏特性以及基因突变特征.方法 选取2022 年1 月至2024 年1月沧州市第三医院收治的 683 例肺结核患者为研究对象,根据药敏实验结果分为耐药组(120 例)和非耐药组(563例).对耐药菌株进行全基因组测序,分析耐药相关基因的突变特征.结果 共检出 120 例耐药结核,耐药率为17.6%,2 组是否初次诊断肺结核、是否存在结核空洞比较,差异有统计学意义(P<0.05).耐药结核分枝杆菌中,单耐药比例62.5%,耐多药比例10.8%,广泛耐药比例 4.2%.基因突变分析显示,异烟肼耐药主要与KatG和inhA基因突变相关,分别占28.3%和10.0%;利福平耐药与rpoB基因突变相关,占 27.5%;链霉素耐药与rpsL和rrs基因突变相关,分别占11.6%和3.4%;乙胺丁醇耐药与embB和embA基因突变相关,分别占 10.0%和 3.3%;OFX耐药与gyrA和gyrB基因突变相关,分别占5.0%和0.8%.突变频率最高的是KatG 基因编码蛋白的第315 位丝氨酸突变为苏氨酸,突变频率为20.8%.北京基因型亚型菌株中inhA基因突变的占比显著低于非北京基因型菌株(P<0.05).结论 耐药性结核分枝杆菌有特定的基因突变模式,突变基因与药物敏感性显著相关.研究结果揭示了耐药结核分枝杆菌的分子机制,为治疗耐药性肺结核的药物选择提供了依据,对耐药结核的精准治疗和预防具有重要意义.
Analysis of Gene Mutations and Drug Susceptibility in Mycobacterium Tu-berculosis Isolates from Patients with Drug-Resistant Pulmonary Tubercu-losis
Objective This study aimed to explore the drug susceptibility and gene mutation profiles of drug-resistant Mycobacterium tuberculosis.Methods A total of 683 pulmonary tuberculosis cases treated at Cangzhou Third Hospital from January 2022 to January 2024 were analyzed.Drug susceptibility testing was conducted using the Roche culture medium pro-portion method,and whole genome sequencing was performed on drug-resistant strains.Results Of the cases,120(17.6%)were drug-resistant.Compare whether the two groups have been diagnosed with tuberculosis for the first time and whether there is a tuberculosis cavity(P<0.05).Mono-drug resistance comprised 62.5%of resistant cases,multidrug re-sistance 10.8%,and extensively drug-resistant TB 4.2%.Gene mutations associated with drug resistance included katG(28.3%)and inhA(10.0%)for isoniazid resistance,rpoB(27.5%)for rifampicin resistance,rpsL(11.6%)and rrs(3.4%)for streptomycin resistance,embB(10.0%)and embA(3.3%)for ethambutol resistance,and gyrA(5.0%)and gyrB(0.8%)for ofloxacin resistance.The most common mutation was a serine-to-threonine substitution at codon 315 of katG(20.8%).Beijing genotype strains had significantly fewer inhA mutations compared to non-Beijing strains(P<0.05).Con-clusion Drug-resistant Mtb strains exhibit specific gene mutation patterns linked to drug resistance,providing insight into treatment selection and the molecular mechanisms of resistance.

Mycobacterium tuberculosisPulmonary tuberculosisDrug resistanceWhole genome sequencingGene mutations

张新园、李继翰、国美峰、倪磊磊、王桂芹

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061001 河北沧州,沧州市第三医院结核二科

061001 河北沧州,沧州市第三医院结核三科

结核分枝杆菌 肺结核 耐药性 全基因组测序 基因突变

2024

转化医学杂志
海军总医院

转化医学杂志

CSTPCD
影响因子:0.671
ISSN:2095-3097
年,卷(期):2024.13(7)