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Whole-genome sequencing as a tool for studying the microevolution of drug-resistant serial Mycobacterium tuberculosis isolates. | LitMetric

AI Article Synopsis

  • Treatment of drug-resistant tuberculosis involves using more toxic and less effective drugs, which can lead to cases of retreatment due to treatment failures or disease recurrence.
  • The study investigated the microevolution of drug resistance in Mycobacterium tuberculosis through serial isolates from six patients, using both phenotypic and genotypic techniques, including whole-genome sequencing.
  • Findings revealed key mutations in resistance-related genes and highlighted the ability of sequencing technologies to identify rare mutations and mixed strain populations, thereby enhancing tuberculosis management by informing timely clinical decisions.

Article Abstract

Treatment of drug-resistant tuberculosis requires extended use of more toxic and less effective drugs and may result in retreatment cases due to failure, abandonment or disease recurrence. It is therefore important to understand the evolutionary process of drug resistance in Mycobacterium tuberculosis. We here in describe the microevolution of drug resistance in serial isolates from six previously treated patients. Drug resistance was initially investigated through phenotypic methods, followed by genotypic approaches. The use of whole-genome sequencing allowed the identification of mutations in the katG, rpsL and rpoB genes associated with drug resistance, including the detection of rare mutations in katG and mixed populations of strains. Molecular docking simulation studies of the impact of observed mutations on isoniazid binding were also performed. Whole-genome sequencing detected 266 single nucleotide polymorphisms between two isolates obtained from one patient, suggesting a case of exogenous reinfection. In conclusion, sequencing technologies can detect rare mutations related to drug resistance, identify subpopulations of resistant strains, and identify diverse populations of strains due to exogenous reinfection, thus improving tuberculosis control by guiding early implementation of appropriate clinical and therapeutic interventions.

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Source
http://dx.doi.org/10.1016/j.tube.2021.102137DOI Listing

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