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

Autor: Emilyn Costa Conceição, Johannes Loubser, Arthur Emil dos Santos Guimarães, Abhinav Sharma, Liliana Kokusanilwa Rutaihwa, Anzaan Dippenaar, Richard Steiner Salvato, Ricardo José de Paula Souza e Guimarães, Maria Cristina da Silva Lourenço, Wandyra Araújo Barros, Ninarosa Calzavara Cardoso, Robin Mark Warren, Sebastien Gagneux, Beatriz Gilda Jegerhorn Grinsztejn, Philip Noel Suffys, Karla Valéria Batista Lima
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Microorganisms, Vol 12, Iss 9, p 1817 (2024)
Druh dokumentu: article
ISSN: 2076-2607
DOI: 10.3390/microorganisms12091817
Popis: 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.
Databáze: Directory of Open Access Journals