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.
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.