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中国甘肃结核分枝杆菌分离株耐药表型和基因型分析。

Phenotypic and genotypic analysis of drug resistance in M. tuberculosis isolates in Gansu, China.

机构信息

Gansu Agricultural University, Lanzhou, Gansu, China.

Lanzhou Maternal and Child Health Care Hospital, Lanzhou, Gansu, China.

出版信息

PLoS One. 2024 Sep 27;19(9):e0311042. doi: 10.1371/journal.pone.0311042. eCollection 2024.

DOI:10.1371/journal.pone.0311042
PMID:39331607
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11432870/
Abstract

Tuberculosis has posed a serious threat to human health. It is imperative to investigate the geographic prevalence of tuberculosis and medication resistance, as this information is essential for informing strategies for its prevention and treatment. Drug resistance was identified using a proportion method. Drug-resistant genes and pathways were predicted using whole genome sequencing. The drug resistance range of bedaquiline was identified using the microporous plate two-fold dilution method, and drug resistance genes were studied using sequencing. The study revealed that 19.99% of the tuberculosis cases had multidrug resistance. The genes of M. tuberculosis are predominantly involved in the synthesis of ABC transporters, two-component systems, and bacterial secretion systems, as well as in energy production and conversion, and lipid transport and metabolism. The genes encode for 82.45% of carbohydrate-related enzymes such as glycoside hydrolases, glycosyl transferases, and carbohydrate esterases. The minimum inhibitory concentration (MIC) of bedaquiline against clinical strains was approximately 0.06 μg/mL, with identified mutations in drug-resistant genes Rv0678, atpE, and pepQ, specifically V152A, P62A, and T222N, respectively. The multidrug resistance tuberculosis development was attributed to the strong medication resistance exhibited. It was concluded that tuberculosis had presented a high level of drug resistance. Phenotypic resistance was related to genes, existing potential genetic resistance in M. tuberculosis. Bedaquiline was found to possess effective antibacterial properties against M. tuberculosis.

摘要

结核病对人类健康构成了严重威胁。调查结核病的地理流行情况和药物耐药性至关重要,因为这些信息对于制定预防和治疗策略至关重要。采用比例法鉴定药物耐药性。使用全基因组测序预测耐药基因和途径。采用微孔板二倍稀释法确定乙胺丁醇的耐药范围,并通过测序研究耐药基因。研究表明,19.99%的结核病病例存在耐多药现象。结核分枝杆菌的基因主要参与 ABC 转运蛋白、双组分系统和细菌分泌系统的合成,以及能量产生和转化、脂质运输和代谢。这些基因编码 82.45%的碳水化合物相关酶,如糖苷水解酶、糖基转移酶和碳水化合物酯酶。乙胺丁醇对临床分离株的最低抑菌浓度(MIC)约为 0.06μg/ml,耐药基因 Rv0678、atpE 和 pepQ 中发现了突变,分别为 V152A、P62A 和 T222N。耐多药结核病的发展归因于其表现出的强烈耐药性。研究结果表明,结核病的耐药程度很高。表型耐药与基因有关,结核分枝杆菌存在潜在的遗传耐药性。乙胺丁醇对结核分枝杆菌具有有效的抗菌作用。

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