Transcriptional Regulator, Metabolic, and Pilus Biosynthesis Genes as Candidate Virulence Markers in High-Virulence Mycobacterium abscessus

Mycobacterium abscessus is a rapidly growing non-tuberculosis mycobacterium that opportunistically causes pulmonary infections and is notable for its high resistance to antibiotics. While ubiquitous in environmental reservoirs such as soil, water, and biofilms, the genetic factors that enable certain strains to invade and persist in human hosts have remained elusive. To address this gap, we compared whole-genome sequences from 45 environmental isolates-- primarily collected on Hawaii Island--with a globally sourced set of clinical isolates retrieved from NCBI RefSeq. Our phylogenetic reconstruction delineated environmental and clinical lineages, and pangenome profiling revealed a conserved core genome of approximately 4,800 genes alongside a large accessory genome. Crucially, we found 20 genes conserved in clinical isolates, but not environmental isolates. Clinical isolates were found to have conserved genes coding for erm(41), three transcriptional regulators, a pilus synthesis gene, an NADP-dependent oxidoreductase, a carbonic anhydrase, a probable L-ectoine synthase, a ribonuclease P protein component, and 11 hypothetical genes, whereas environmental isolated did not conserve any of these genes. This indicates that clinical isolates have undergone broad changes relating to metabolism, pilus biosynthesis, and transcriptional regulators, which may be necessary for pathogenicity. The candidate virulence markers uncovered here lay the groundwork for experimental validation, rapid diagnostics for non-tuberculous mycobacteria, and targeted surveillance of environmental reservoirs to mitigate the emergence of clinically significant strains. ImportanceMycobacterium abscessus is an emerging pathogen that causes pulmonary infections in susceptible individuals. Though currently an opportunistic pathogen, M. abscessus may be undergoing evolutionary changes to become an obligate pathogen. Because of this, there is the need to identify markers of virulence in M. abscessus in order to better screen isolates and assess their risk of causing infection. This also provides the opportunity to study a similar pathogenesis to what Mycobacterium tuberculosis may have undergone. This study revealed that clinical isolates of M. abscessus have conserved genes relating to pilus biosynthesis, metabolism, and transcriptional regulators that environmental isolates do not have. These conserved genes may be required for M. abscessus to acquire virulence, and these genes have potential use as biomarkers to screen isolates for possible pathogenicity.