A genome-focused investigation reveals the emergence of a mycobacterium tuberculosis strain related to multidrug-resistant tuberculosis in the Amazon region of Brazil

Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Programa de Pós-Graduação em Pesquisa Clínica em Doenças Infecciosas. Rio de Janeiro, RJ, Brasil / Stellenbosch University. Faculty of Medicine and Health Sciences. Division of Molecular Biology and Human Genetics. Centre for Tuberculosis Research. South African Medical Research Council. Centre of Excellence for Biomedical Tuberculosis Research. National Research Foundation. Department of Science and Innovation. Cape Town, Western Cape, South Africa.
Stellenbosch University. Faculty of Medicine and Health Sciences. Division of Molecular Biology and Human Genetics. Centre for Tuberculosis Research. South African Medical Research Council. Centre of Excellence for Biomedical Tuberculosis Research. National Research Foundation. Department of Science and Innovation. Cape Town, Western Cape, South Africa.
Universidade do Estado do Pará. Centro de Ciências Biológicas e da Saúde. Programa de Pós-Graduação em Biologia Parasitária na Amazônia. Belém, PA, Brasil.
Stellenbosch University. Faculty of Medicine and Health Sciences. Division of Molecular Biology and Human Genetics. Centre for Tuberculosis Research. South African Medical Research Council. Centre of Excellence for Biomedical Tuberculosis Research. National Research Foundation. Department of Science and Innovation. Cape Town, Western Cape, South Africa.
Swiss Tropical and Public Health Institute. Allschwil, Switzerland / University of Basel. Basel, Switzerland.
Stellenbosch University. Faculty of Medicine and Health Sciences. Division of Molecular Biology and Human Genetics. Centre for Tuberculosis Research. South African Medical Research Council. Centre of Excellence for Biomedical Tuberculosis Research. National Research Foundation. Department of Science and Innovation. Cape Town, Western Cape, South Africa / University of Antwerp. Faculty of Medicine and Health Sciences. Family Medicine and Population Health. Antwerp, Belgium.
Universidade Federal do Rio Grande do Sul. Centro de Biotecnologia. Programa de Pós-Graduação em Biologia Celular e Molecular. Porto Alegre, RS, Brasil.
Instituto Evandro Chagas. Seção de Epidemiologia. Ananindeua, PA, Brasil.
Stellenbosch University. Faculty of Medicine and Health Sciences. Division of Molecular Biology and Human Genetics. Centre for Tuberculosis Research. South African Medical Research Council. Centre of Excellence for Biomedical Tuberculosis Research. National Research Foundation. Department of Science and Innovation. Cape Town, Western Cape, South Africa / Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Bacteriologia e Bioensaios. Rio de Janeiro, RJ, Brasil.
Universidade do Estado do Pará. Complexo Hospitalar. Hospital Universitário João de Barros Barreto. Belém, PA, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular Aplicada a Micobactérias. Rio de Janeiro, RJ, Brasil.
Stellenbosch University. Faculty of Medicine and Health Sciences. Division of Molecular Biology and Human Genetics. Centre for Tuberculosis Research. South African Medical Research Council. Centre of Excellence for Biomedical Tuberculosis Research. National Research Foundation. Department of Science and Innovation. Cape Town, Western Cape, South Africa.
Swiss Tropical and Public Health Institute. Allschwil, Switzerland / University of Basel. Basel, Switzerland.
Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular Aplicada a Micobactérias. Rio de Janeiro, RJ, Brasil.
Universidade do Estado do Pará. Centro de Ciências Biológicas e da Saúde. Belém, PA, Brasil / Instituto Evandro Chagas. Seção de Bacteriologia e Micologia. Ananindeua, PA, Brasil.

Resumo em Inglês

A previous study in Pará, Northern Brazil, described a strain of Mycobacterium tuberculosis with a unique genotype (SIT2517/T1) associated with multidrug-resistant tuberculosis (MDR-TB). To improve our understanding of MDR-TB transmission dynamics of these strains within this region, we performed phenotypic and genotypic drug susceptibility testing (pDST/gDST), 24-loci mycobacterial interspersed repetitive units (MIRU-VNTR) genotyping, whole-genome sequencing (WGS) and geo-epidemiology analysis. Of the 28 SIT2517/T1 isolates, 19 (67.9%) could be genotyped by 24-loci MIRU-VNTR and 15 by WGS. All belonged to sublineage 4.1.1.3, distinct from other representative Lineage 4 isolates identified in Brazil. The MDR phenotype determined by pDST was confirmed by gDST, the latter also demonstrating the presence of additional mutations conferring pre-extensively drug-resistance (pre-XDR). Discrepancies between gDST and pDST were observed for pyrazinamide and fluoroquinolones. Thirteen out of 15 isolates analyzed by WGS were clustered when applying a 12 single nucleotide polymorphisms (SNPs) cutoff. The SIT2517/T1 isolates were distributed across the metropolitan regions of Belém and Collares municipalities, showing no geographic clustering. WGS-transmission network analysis revealed a high likelihood of direct transmission and the formation of two closely linked transmission chains. This study highlights the need to implement TB genomic surveillance in the Brazilian Amazon region.

Palavras-chave em inglês

Tuberculosis
Multidrug-resistant
Whole-genome sequencing
Genotype emergence
MIRU-VNTR
Lineage

Editor

MDPI

Referência

CONCEIÇÃO, Emilyn Costa et al. A genome-focused investigation reveals the emergence of a mycobacterium tuberculosis strain related to multidrug-resistant tuberculosis in the Amazon region of Brazil. Microorganisms, v. 12, n. 9, p. 1-13, 2 Sept. 2024.

DOI

10.3390/microorganisms12091817

ISSN

2076-2607

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Produção científica do Laboratório de Biologia Molecular Aplicada a Micobactérias.

Use este identificador para citar ou linkar para este item: https://www.arca.fiocruz.br/handle/icict/66174

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