Mycobacterium abscessus (MAB), a rapidly growing non-tuberculous mycobacteria, can cause infections in both immunocompetent and immunocompromised individuals. While global attention remains focused on Mycobacterium tuberculosis, in-depth research for MAB is imperative due to the increased incidence of infections globally, inherent and acquired resistance to conventional and anti-TB drugs, lateral gene transfer and a recently discovered potential for human-to-human transmission. We aim to identify geographic patterns of genomic signatures associated with antibiotic resistance and virulence in MAB. To achieve this objective, we have developed an ensemble strategy for comprehending antimicrobial resistance (AMR) and virulence in MAB, by employing a pan-genome of more than 1000 whole genome sequences. Through an exploration of the genomic landscape of MAB, we aim to identify global and local determinants of antibiotic resistance and virulence. The study also investigates drivers of horizontal gene transfer, considering the genomic mosaicism in MAB. Additionally, we emphasize the identification of invariant proteins for potential drug targets in MAB. Our focus extends to analysing the population structure of MAB to understand transmission in the context of antibiotic resistance. Our research reveals a constantly evolving nature of MAB with an open pangenome. We've extensively annotated the MAB genomes in the context of antibiotic resistance and virulence. Our findings suggest a need to rethink empirical antibiotic therapy strategies at the local level, recognizing the local drug resistance patterns. This shift can improve our approach in addressing antibiotic resistance in MAB.

An ensemble approach to studying antimicrobial resistance in non-tuberculous mycobacteria, specifically <i>Mycobacterium abscessus</i> (MAB), involves deeply annotating MAB genomes and highlighting the global distribution patterns of AMR genes. We advocate for a localized understanding of resistance profiles, as this approach is pivotal in devising targeted strategies to address the burgeoning threat of AMR.

An ensemble approach to studying antimicrobial resistance in non-tuberculous mycobacteria, specifically Mycobacterium abscessus (MAB), involves deeply annotating MAB genomes and highlighting the global distribution patterns of AMR genes. We advocate for a localized understanding of resistance profiles, as this approach is pivotal in devising targeted strategies to address the burgeoning threat of AMR.

Simran Gambhir

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