Genomics of nontuberculous mycobacteria NTM: development of a laboratory tool for rapid and precise diagnosis and surveillance of NTM infections

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Genome-Scale Characterization of Mycobacterium abscessus Complex Isolates from Portugal

Publication . Carneiro, Sofia; Pinto, Miguel; Silva, Sónia; Santos, Andrea; Rodrigues, Irene; Santos, Daniela; Duarte, Sílvia; Vieira, Luís; Gomes, João Paulo; Macedo, Rita

The Mycobacterium abscessus complex (MABC) is an emerging, difficult to treat, multidrug-resistant nontuberculous mycobacteria responsible for a wide spectrum of infections and associated with an increasing number of cases worldwide. Dominant circulating clones (DCCs) of MABC have been genetically identified as groups of strains associated with higher prevalence, higher levels of antimicrobial resistance, and worse clinical outcomes. To date, little is known about the genomic characteristics of MABC species circulating in Portugal. Here, we examined the genetic diversity and antimicrobial resistance profiles of 30 MABC strains isolated between 2014 and 2022 in Portugal. The genetic diversity of circulating MABC strains was assessed through a gene-by-gene approach (wgMLST), allowing their subspecies differentiation and the classification of isolates into DCCs. Antimicrobial resistance profiles were defined using phenotypic, molecular, and genomic approaches. The majority of isolates were resistant to at least two antimicrobials, although a poor correlation between phenotype and genotype data was observed. Portuguese genomes were highly diverse, and data suggest the existence of MABC lineages with potential international circulation or cross-border transmission. This study highlights the genetic diversity and antimicrobial resistance profile of circulating MABC isolates in Portugal while representing the first step towards the implementation of a genomic-based surveillance system for MABC at the Portuguese NIH.

2023-10-20Journal article

Open access

Genome-scale analysis of Mycobacterium avium complex isolates from Portugal reveals extensive genetic diversity

Publication . Carneiro, Sofia; Pinto, Miguel; Rodrigues, Joana; Gomes, João Paulo; Macedo, Rita

Opportunist infections caused by nontuberculous mycobacteria (NTM) have emerged as a significant public health problem. Among these, species of the Mycobacterium avium complex (MAC) are the main responsible for the increase in the number of human disease cases. In order to address the current needs in the detection and surveillance of MAC disease cases, we evaluated different species classification methodologies (BLASTn-based marker-gene approach, Kraken v2, rMLST and MLST databases) and their congruence with a core-SNP phylogenetic approach, based on whole genome sequencing (WGS) data. For this purpose, we used a collection of 142 MAC isolates from Portuguese patients diagnosed between 2014 and 2022. The marker-gene approach (based on the rpoB, hsp65 and groEL genes), showed the best results, allowing the identification of the 142 MAC isolates to the species/subspecies level (M. avium subsp. hominissuis, M. intracellulare, M. intracellulare subsp. chimaera, M. intracellulare subsp. yongonense, M. marseillence and M. colombiense). Additionally, we performed drug susceptibility testing that confirmed clarithromycin efficacy as a first-line treatment for MAC disease, as 93 % of the Portuguese isolates were susceptible. Using a core-SNP approach we also performed an in-depth phylogenetic analysis within each identified species group, and despite the high genetic diversity within the MAC species, we were able to clearly distinguish all the species/subspecies and identify genetic clusters with epidemiological potential. We highlight not only the need for the standardization of an appropriate genotyping approach for species identification and management of MAC disease, but also a more robust large-scale WGS data analysis, in a One Health perspective, in order to identify potential routes of transmission.

2024-10-20Research article

Open access