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Home / Publicações / Whole-genome sequencing as a tool for studying the microevolution of drug-resistant serial Mycobacterium tuberculosis isolates

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

  • Autores: Jaciara de Lourdes do Carmo Guimarães Diniz, Andrea von Groll, Gisela Unis, Elis Regina Dalla Costa, Maria Lucia Rosa Rossetti, Júlia Silveira Vianna, Daniela Fernandes Ramos, Ana Júlia Reis, Priscila Cristina Bartolomeu Halicki, João Luis Rheingantz Scaini, Yasmin Castillos de Ibrahim das Neves, Jody Phelan, Ana Rita Gomes, Susana Campino, Karina dos Santos Machado, Adriano Velasque Werhli, Arnab Pain, Taane Gregory Clark, João Perdigão, Miguel Viveiros, Isabel Portugal, Pedro Eduardo Almeida Silva
  • Ano de Publicação: 2021
  • Journal: Tuberculosis, vol 131, art 102137
  • Link: https://doi.org/10.1016/j.tube.2021.102137

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.

KEYWORDS

Catalase assay; Exogenous reinfection; Microevolution; Resistance; Whole-genome sequencing.

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    About GHTM

    GHTM is a R&D Center that brings together researchers from IHMT with a track record in Tropical Medicine and International/Global Health. It aims at strengthening Portugal's role as a leading partner in the development and implementation of a global health research agenda. Our evidence-based interventions contribute to the promotion of equity in health and to improve the health of populations.

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