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Updated: Jan 18, 2026
A Microscopic Phenotypic Assay for the Quantification of Intracellular Mycobacteria Adapted for High-throughput/High-content Screening
Published on: January 17, 2014
Within-host population dynamics of extensively drug-resistant Mycobacterium tuberculosis revealed by an over 3-year
Peng Xu1, Xuecong Zhang1, Chi Wu2
1National Clinical Research Center for Infectious Diseases, Shenzhen Clinical Research Center for Tuberculosis, Shenzhen Third People's Hospital, Shenzhen, China.
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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