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ORIGINAL RESEARCH article

Front. Microbiol.

Sec. Antimicrobials, Resistance and Chemotherapy

Volume 16 - 2025 | doi: 10.3389/fmicb.2025.1663069

This article is part of the Research TopicMaterials, Adaptation, and Evolution: How Anthropogenic Activities Impact Microbial ResistanceView all 4 articles

Drug Selection based on Pan-genomics genetic features of Mycobacterium tuberculosis

Provisionally accepted
Xiangcheng  SunXiangcheng SunPanpan  XuPanpan XuYun  ShiYun ShiNing  WangNing WangYan  LiYan Li*
  • West China Hospital, Sichuan University, Chengdu, China

The final, formatted version of the article will be published soon.

Tuberculosis, caused by Mycobacterium tuberculosis, is a severe and persistent global public health issue, particularly exacerbated by the emergence of multidrug-resistant and extensively drug-resistant strains. This study employed pan-genomic approaches to analyze different strains with various resistance profiles, examining the diversity of bacterial genetic evolution in relation to mutations in resistance-related genes. The findings indicate that resistance-related genes are mostly core genes (94%), with a preference for base mutations closely associated with nonsynonymous mutations at resistance sites. Interestingly, while the majority of drugs induce positive selection in target genes, the tlyA gene under the influence of Amikacin (AMI) undergoes passive selection. Cluster analysis of target genes suggests consistency between SNP clusters and drug-resistant clusters, revealing a strong correlation between bacterial evolutionary branches and resistance profiles. Consequently, based on pan-genome evolutionary characteristics, we identified the drug-resistant mutation pattern (DRMP) that can serve as a molecular fingerprint and indicator for drug sensitivity, aiding in the assessment and guidance of drug selection for treating different strains and the formulation of individualized treatment plans. This research not only enhances our understanding of the mechanisms of drug resistance in M. tuberculosis but also offers new perspectives for the development of new drugs, which is crucial for global tuberculosis control.

Keywords: M. tuberculosis, Drug Resistance, genetic diversity, DRMP, therapeutic andcontrol strategies

Received: 10 Jul 2025; Accepted: 21 Aug 2025.

Copyright: © 2025 Sun, Xu, Shi, Wang and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Yan Li, West China Hospital, Sichuan University, Chengdu, China

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