Within-host population dynamics of extensively drug-resistant Mycobacterium tuberculosis revealed by an over 3-year longitudinal study.

IF 2.1 3区 医学 Q2 EVOLUTIONARY BIOLOGY
Evolution, Medicine, and Public Health Pub Date : 2025-07-01 eCollection Date: 2025-01-01 DOI:10.1093/emph/eoaf014
Peng Xu, Xuecong Zhang, Chi Wu, Yiwang Chen, Wenjie Lai, Liyong Liu, Jialei Liang, Dan Li, Ruimin Hong, Senlin Zhan, Peize Zhang, Howard Takiff, Guofang Deng, Jiuxin Qu, Qian Gao
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引用次数: 0

Abstract

Background and objectives: Drug resistance is a major contributor to tuberculosis (TB) deaths worldwide. Understanding the dynamics of in-host evolution of Mycobacterium tuberculosis (MTB) drug resistance can help to improve treatment success rates.

Methodology: The microevolution of drug-resistant MTB was studied in three patients with long-standing, extensively drug-resistant TB (XDR-TB) by analyzing whole genome sequences of serial isolates collected during treatment.

Results: We identified three patterns of in vivo MTB microevolution during long-term, ineffective treatment: (i) new drug-resistant subpopulations emerge and compete with other subpopulations during treatment; (ii) drug resistance profiles remaining stable without the emergence of new drug-resistant subpopulations; and (iii) after a drug is stopped, new drug-resistant subpopulations continue to emerge and compete with existing subpopulations.

Conclusions and implications: The microevolution of drug-resistant MTB within patients on long-term ineffective treatment is complex. Subpopulations with different resistance-conferring mutations can compete with each other and with newly emerged subpopulations. Often, one subpopulation eventually dominates and achieves long-term stability. This work deepens the understanding of MTB microevolution in XDR-TB patients.

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一项超过3年的纵向研究揭示了广泛耐药结核分枝杆菌宿主种群动态。
背景和目的:耐药性是全世界结核病死亡的一个主要原因。了解结核分枝杆菌(MTB)耐药在宿主内进化的动态有助于提高治疗成功率。方法:通过分析治疗期间收集的系列分离株的全基因组序列,研究了3例长期广泛耐药结核病(XDR-TB)患者耐药MTB的微进化。结果:在长期无效治疗期间,我们确定了三种体内MTB微进化模式:(i)在治疗期间出现新的耐药亚群并与其他亚群竞争;(ii)在没有出现新的耐药亚群的情况下,耐药概况保持稳定;(iii)停药后,新的耐药亚群继续出现并与现有的亚群竞争。结论和意义:长期无效治疗的耐药MTB患者的微进化是复杂的。具有不同抗性突变的亚种群可以相互竞争,也可以与新出现的亚种群竞争。通常,一个亚种群最终占主导地位并实现长期稳定。这项工作加深了对广泛耐药结核病患者MTB微进化的理解。
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来源期刊
Evolution, Medicine, and Public Health
Evolution, Medicine, and Public Health Environmental Science-Health, Toxicology and Mutagenesis
CiteScore
5.40
自引率
2.70%
发文量
37
审稿时长
8 weeks
期刊介绍: About the Journal Founded by Stephen Stearns in 2013, Evolution, Medicine, and Public Health is an open access journal that publishes original, rigorous applications of evolutionary science to issues in medicine and public health. It aims to connect evolutionary biology with the health sciences to produce insights that may reduce suffering and save lives. Because evolutionary biology is a basic science that reaches across many disciplines, this journal is open to contributions on a broad range of topics.
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