The relationships of gene mutations between ESX and drug resistance in the patients with extra-pulmonary tuberculosis in local regions of Southwest China

IF 2.6 4区医学 Q3 INFECTIOUS DISEASES

Infection Genetics and Evolution Pub Date : 2025-07-17 DOI:10.1016/j.meegid.2025.105799

Jiwen Fan , Haoming Feng , Dazhi Yang , Haiyang Zhao , Tao Shi , Tongxin Li

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引用次数: 0

Abstract

Background

Drug resistant extrapulmonary tuberculosis (DR-EPTB) is a major threat to human health. The mycobacterial ESAT-6 secretion (ESX) system is main virulence protein export system of Mycobacterium tuberculosis (MTB). This study aimed to determine the relationships between ESX and drug resistance (DR) in patients with DR-EPTB in local regions of Southwest China.

Methods and design

Patients were retrospectively studied from January 2020 to December 2021. All the isolates were cultured, drug susceptibility was detected, and gene mutations were detected using whole-genome sequencing (WGS). The correlations between the mutant genes of the ESX system and DR pattern, patient demographics, and DR mutant gene sites were analyzed.

Results

A total of 111 patients with DR-EPTB were enrolled including 40 females and 71 males. In the five ESX systems there were 1664 gene mutation sites and ESX-3 accounted for 32.6 %. The most common mutant gene site in all the ESX systems was eccC2. There was a significant difference in the number of mutant gene sites between ESX-1 and DR (P < 0.01). There were significant correlations between the numbers of mutant gene sites in the different ESX systems and gender (P < 0.05), age group (P < 0.05), residence (P < 0.01), type of treatment (P < 0.01), lineage (P < 0.01) and cluster (P < 0.01).

Conclusion

In patients with DR-EPTB, ESX-3 was the system that included the most mutant gene sites and the eccC2 gene had the highest frequency. The gender, age group, residence, type of treatment, lineage and cluster were risk factors for gene mutations in the ESX system. The mutant gene sites of ESX-1 were correlated with those of DR and the mutations in espA and espK may be the main factors.

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西南地区肺外结核患者ESX基因突变与耐药的关系

背景：耐药肺外结核（DR-EPTB）是威胁人类健康的主要疾病。分枝杆菌ESAT-6分泌系统（ESX）是结核分枝杆菌（MTB）主要的毒力蛋白输出系统。本研究旨在确定西南地区耐药eptb患者ESX与耐药（DR）之间的关系。方法和设计：从2020年1月至2021年12月对患者进行回顾性研究。对所有分离株进行培养、药敏检测和基因突变全基因组测序（WGS）。分析ESX系统突变基因与DR模式、患者人口统计学和DR突变基因位点之间的相关性。结果：共纳入DR-EPTB患者111例，其中女性40例，男性71例。5个ESX系统共有1664个基因突变位点，其中ESX-3占32.6 %。所有ESX系统中最常见的突变基因位点是eccC2。结论：DR- eptb患者中，ESX-3是突变基因位点最多的系统，eccC2基因频率最高。性别、年龄组、居住地、治疗类型、谱系和聚类是ESX系统基因突变的危险因素。ESX-1突变位点与DR突变位点相关，espA和espK突变可能是主要影响因素。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Infection Genetics and Evolution 医学-传染病学

CiteScore

8.40

自引率

0.00%

发文量

215

审稿时长

82 days

期刊介绍： (aka Journal of Molecular Epidemiology and Evolutionary Genetics of Infectious Diseases -- MEEGID) Infectious diseases constitute one of the main challenges to medical science in the coming century. The impressive development of molecular megatechnologies and of bioinformatics have greatly increased our knowledge of the evolution, transmission and pathogenicity of infectious diseases. Research has shown that host susceptibility to many infectious diseases has a genetic basis. Furthermore, much is now known on the molecular epidemiology, evolution and virulence of pathogenic agents, as well as their resistance to drugs, vaccines, and antibiotics. Equally, research on the genetics of disease vectors has greatly improved our understanding of their systematics, has increased our capacity to identify target populations for control or intervention, and has provided detailed information on the mechanisms of insecticide resistance. However, the genetics and evolutionary biology of hosts, pathogens and vectors have tended to develop as three separate fields of research. This artificial compartmentalisation is of concern due to our growing appreciation of the strong co-evolutionary interactions among hosts, pathogens and vectors. Infection, Genetics and Evolution and its companion congress [MEEGID](http://www.meegidconference.com/) (for Molecular Epidemiology and Evolutionary Genetics of Infectious Diseases) are the main forum acting for the cross-fertilization between evolutionary science and biomedical research on infectious diseases. Infection, Genetics and Evolution is the only journal that welcomes articles dealing with the genetics and evolutionary biology of hosts, pathogens and vectors, and coevolution processes among them in relation to infection and disease manifestation. All infectious models enter the scope of the journal, including pathogens of humans, animals and plants, either parasites, fungi, bacteria, viruses or prions. The journal welcomes articles dealing with genetics, population genetics, genomics, postgenomics, gene expression, evolutionary biology, population dynamics, mathematical modeling and bioinformatics. We also provide many author benefits, such as free PDFs, a liberal copyright policy, special discounts on Elsevier publications and much more. Please click here for more information on our author services .