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

• Published in: Microorganisms (Basel) Vol. 12; no. 9; p. 1817
• Main Authors: Conceição, Emilyn Costa, Loubser, Johannes, Guimarães, Arthur Emil Dos Santos, Sharma, Abhinav, Rutaihwa, Liliana Kokusanilwa, Dippenaar, Anzaan, Salvato, Richard Steiner, de Paula Souza E Guimarães, Ricardo José, da Silva Lourenço, Maria Cristina, Barros, Wandyra Araújo, Cardoso, Ninarosa Calzavara, Warren, Robin Mark, Gagneux, Sebastien, Grinsztejn, Beatriz Gilda Jegerhorn, Suffys, Philip Noel, Lima, Karla Valéria Batista
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 02.09.2024; MDPI
• Subjects: Analysis; Automation; Chromosomes; Clustering; Disease transmission; Drug resistance; Epidemiology; Fluoroquinolones; Gene sequencing; Genetic aspects; Genomes; Genomic analysis; Genomics; Genotype & phenotype; genotype emergence; Genotyping; Geographic information systems; Geographical distribution; Investigations; lineage; Metropolitan areas; MIRU-VNTR; Multidrug resistance; multidrug-resistant; Mycobacterium tuberculosis; Network analysis; Nucleotides; Phenotypes; Phylogenetics; Public health; Pyrazinamide; Quality control; Single nucleotide polymorphisms; Single-nucleotide polymorphism; Software; Tuberculosis; Whole genome sequencing; Brazil; United States > US; lineage; genotype emergence; MIRU-VNTR; whole-genome sequencing; tuberculosis; multidrug-resistant
• ISSN: 2076-2607; 2076-2607
• DOI: 10.3390/microorganisms12091817

A previous study in Pará, Northern Brazil, described a strain of 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.