A Genome-Focused Investigation Reveals the Emergence of a Mycobacterium tuberculosis Strain Related to Multidrug-Resistant Tuberculosis in the Amazon Region of Brazil
A previous study in Pará, Northern Brazil, described a strain of <i>Mycobacterium tuberculosis</i> 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.
Authors
- Emilyn Costa Conceição (ORCID: https://orcid.org/0000-0002-7445-6620)
- Richard Steiner Salvato (ORCID: https://orcid.org/0000-0002-5701-9437)
- Robin M. Warren (ORCID: https://orcid.org/0000-0001-5741-7358)
- Beatriz Gilda Jegerhorn Grinsztejn (ORCID: https://orcid.org/0000-0003-3692-5155)
- Abhinav Sharma (ORCID: https://orcid.org/0000-0002-6402-6993)
- Ricardo José de Paula Souza e Guimarães (ORCID: https://orcid.org/0000-0002-5767-4765)
- Arthur Emil dos Santos Guimarães
- Anzaan Dippenaar (ORCID: https://orcid.org/0000-0002-2511-7534)
- Philip Noël Suffys (ORCID: https://orcid.org/0000-0001-8527-9300)
- Johannes Loubser (ORCID: https://orcid.org/0000-0002-2362-0187)
- Karla Valéria Batista Lima (ORCID: https://orcid.org/0000-0001-5807-0392)
- Wandyra Araújo Barros
- Sébastien Gagneux (ORCID: https://orcid.org/0000-0001-7783-9048)
- Liliana K. Rutaihwa (ORCID: https://orcid.org/0000-0002-4092-2291)
- Maria Cristina da Silva Lourenço
- Ninarosa Calzavara Cardoso
Institutions
- South African Medical Research Council (ZA)
- Universidade Federal do Rio Grande do Sul (BR)
- University of Antwerp (BE)
- Swiss Tropical and Public Health Institute (CH)
- University of Basel (CH)
- Universidade do Estado do Pará (BR)
- Stellenbosch University (ZA)
- Instituto Evandro Chagas (BR)
- Fundação Oswaldo Cruz (BR)
- Universidade Federal do Pará (BR)
- National Research Foundation (ZA)
Publication Details
- Journal
- Microorganisms
- Published
- 2024-09-02
- DOI
- https://doi.org/10.3390/microorganisms12091817
- Citations
- 3
- Primary Topic
- Tuberculosis Research and Epidemiology
- Type
- article
- Field-Weighted Citation Impact
- 1.17
Funders
- Universidade Federal do Pará