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

Autor: de Lourdes do Carmo Guimarães Diniz J; Núcleo de Pesquisa em Microbiologia Médica, Faculdade de Medicina, Universidade Federal do Rio Grande, Rio Grande, Rio Grande do Sul, Brazil. Electronic address: jaciara_1988@hotmail.com., von Groll A; Núcleo de Pesquisa em Microbiologia Médica, Faculdade de Medicina, Universidade Federal do Rio Grande, Rio Grande, Rio Grande do Sul, Brazil., Unis G; Hospital Sanatório Partenon, Secretaria Estadual de Saúde do Rio Grande do Sul (HSP SES/RS), Porto Alegre, Rio Grande do Sul, Brazil., Dalla-Costa ER; Centro de Desenvolvimento Científico e Tecnológico, Porto Alegre, Rio Grande do Sul, Brazil., Rosa Rossetti ML; Programa de Pós-graduação em Biologia Celular e Molecular, Universidade Luterana do Brasil, Porto Alegre, Brazil., Vianna JS; Núcleo de Pesquisa em Microbiologia Médica, Faculdade de Medicina, Universidade Federal do Rio Grande, Rio Grande, Rio Grande do Sul, Brazil., Ramos DF; Núcleo de Pesquisa em Microbiologia Médica, Faculdade de Medicina, Universidade Federal do Rio Grande, Rio Grande, Rio Grande do Sul, Brazil., Reis AJ; Núcleo de Pesquisa em Microbiologia Médica, Faculdade de Medicina, Universidade Federal do Rio Grande, Rio Grande, Rio Grande do Sul, Brazil., Bartolomeu Halicki PC; Núcleo de Pesquisa em Microbiologia Médica, Faculdade de Medicina, Universidade Federal do Rio Grande, Rio Grande, Rio Grande do Sul, Brazil., Rheingantz Scaini JL; Combi-Lab - Grupo de Biologia Computacional, Centro de Ciências Computacionais C3, Universidade Federal do Rio Grande, Rio Grande, Rio Grande do Sul, Brazil., Castillos de Ibrahim das Neves Y; Núcleo de Pesquisa em Microbiologia Médica, Faculdade de Medicina, Universidade Federal do Rio Grande, Rio Grande, Rio Grande do Sul, Brazil., Phelan J; London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, United Kingdom., Gomes AR; London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, United Kingdom., Campino S; London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, United Kingdom., Machado KDS; Combi-Lab - Grupo de Biologia Computacional, Centro de Ciências Computacionais C3, Universidade Federal do Rio Grande, Rio Grande, Rio Grande do Sul, Brazil., Werhli AV; Combi-Lab - Grupo de Biologia Computacional, Centro de Ciências Computacionais C3, Universidade Federal do Rio Grande, Rio Grande, Rio Grande do Sul, Brazil., Pain A; Pathogen Genomics Laboratory, BESE Division, King Abdullah University of Science and Technology (KAUST), Thuwal, Saudi Arabia; Research Center for Zoonosis Control, Global Institution for Collaborative Research and Education (GI-CoRE), Hokkaido University, Sapporo, Japan., Clark TG; London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, United Kingdom., Perdigão J; Research Institute for Medicines - iMed.ULisboa, Faculdade de Farmácia, Universidade de Lisboa, Lisboa, Portugal., Viveiros M; Unidade de Microbiologia Médica, Global Health and Tropical Medicine, GHTM, Instituto de Higiene e Medicina Tropical, IHMT, Universidade Nova de Lisboa, UNL, Lisboa, Portugal., Portugal I; Research Institute for Medicines - iMed.ULisboa, Faculdade de Farmácia, Universidade de Lisboa, Lisboa, Portugal., Almeida Silva PE; Núcleo de Pesquisa em Microbiologia Médica, Faculdade de Medicina, Universidade Federal do Rio Grande, Rio Grande, Rio Grande do Sul, Brazil.
Jazyk: angličtina
Zdroj: Tuberculosis (Edinburgh, Scotland) [Tuberculosis (Edinb)] 2021 Dec; Vol. 131, pp. 102137. Date of Electronic Publication: 2021 Oct 04.
DOI: 10.1016/j.tube.2021.102137
Abstrakt: 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.
(Copyright © 2021 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: