A Genome-Focused Investigation Reveals the Emergence of a Mycobacterium tuberculosis Strain Related to Multidrug-Resistant Tuberculosis in the Amazon Region of Brazil-Reference-Cited by-同舟云学术

A Genome-Focused Investigation Reveals the Emergence of a Mycobacterium tuberculosis Strain Related to Multidrug-Resistant Tuberculosis in the Amazon Region of Brazil

Published:2024-09-02 Issue:9 Volume:12 Page:1817
ISSN:2076-2607
Container-title:Microorganisms
language:en
Short-container-title:Microorganisms

Author:

Conceição Emilyn Costa¹²^ORCID,Loubser Johannes²^ORCID,Guimarães Arthur Emil dos Santos³,Sharma Abhinav²,Rutaihwa Liliana Kokusanilwa⁴⁵,Dippenaar Anzaan²⁶,Salvato Richard Steiner⁷^ORCID,de Paula Souza e Guimarães Ricardo José⁸^ORCID,da Silva Lourenço Maria Cristina²⁹,Barros Wandyra Araújo¹⁰,Cardoso Ninarosa Calzavara¹¹,Warren Robin Mark²,Gagneux Sebastien⁴⁵,Grinsztejn Beatriz Gilda Jegerhorn¹,Suffys Philip Noel¹¹,Lima Karla Valéria Batista³¹²

Affiliation:

1. Programa de Pós-Graduacao em Pesquisa Clinica e Doencas Infecciosas, Instituto Nacional de Infectologia Evandro Chagas, Fundacao Oswaldo Cruz, Manguinhos, Rio de Janeiro 21046-360, RJ, Brazil

2. Department of Science and Innovation-National Research Foundation Centre of Excellence for Biomedical Tuberculosis Research, South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town 7505, Western Cape, South Africa

3. Programa de Pos-Graduacao Biologia Parasitaria na Amazonia, Universidade do Estado do Para, Belém 66075-110, PA, Brazil

4. Swiss Tropical and Public Health Institute, 4123 Allschwil, Switzerland

5. University of Basel, 4001 Basel, Switzerland

6. Family Medicine and Population Health, Faculty of Medicine and Health Sciences, University of Antwerp, 2610 Antwerp, Belgium

7. Programa de Pós-Graduacao em Biologia Celular e Molecular, Universidade Federal do Rio Grande do Sul, Porto Alegre 90010-150, RS, Brazil

8. Secao de Epidemiologia, Instituto Evandro Chagas, Ananindeua 67030-000, PA, Brazil

9. Laboratório de Bacteriologia e Bioensaios em Micobacterias, Instituto Nacional de Infectologia Evandro Chagas, Fundacao Oswaldo Cruz, Manguinhos, Rio de Janeiro 21046-360, RJ, Brazil

10. Hospital Universitario Joao de Barros Barreto, Universidade Federal do Pará, Belém 66073-000, PA, Brazil

11. Laboratório de Biologia Molecular Aplicada a Micobacteria, Instituto Oswaldo Cruz, Fundacao Oswaldo Cruz, Rio de Janeiro 21046-360, RJ, Brazil

12. Seção de Bacteriologia e Micologia, Instituto Evandro Chagas, Ananindeua 67030-000, PA, Brazil

Abstract

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.

Funder

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Instituto Evandro Chagas (IEC), and the Swiss National Science Foundation

Research Foundation Flanders

South African Medical Research Council (SAMRC), and the Stellenbosch University Faculty of Medicine Health Sciences

Publisher

MDPI AG

Link

https://www.mdpi.com/2076-2607/12/9/1817/pdf

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