Predicting Mycobacterium abscessus proteins with atypical amino acid composition essential for human infections

Abstract

Mycobacterium abscessus is an emerging opportunistic pathogen that causes chronic, difficult-to-treat lung infections, particularly in individuals with underlying lung disease or immune suppression. Despite its clinical significance, the fundamental biological systems of M. abscessus remain poorly understood due to limited research on this organism. Proteins that are unique to an organism are likely to contribute to the organisms distinctive phenotypic traits. Therefore, we initiated this study by identifying proteins with unique features, hypothesizing that such proteins could be critical for M. abscessus pathogenesis. To identify these proteins, we analyzed the genome sequence of the laboratory reference strain using bioinformatics tools to detect proteins with unusual amino acid compositions. We then examined the genomes of a large collection of patient-derived M. abscessus isolates to predict proteins essential for the pathogens ability to cause disease in humans. Our analysis identified 10 proteins--MAB_0010, MAB_0039, MAB_1134, MAB_1602, MAB_1657, MAB_3052, MAB_3131, MAB_3413, MAB_4263, and MAB_4537--that exhibit restricted evolutionary variation in human infections, similar to five known essential proteins DnaA, DnaN, RpoA, RpoB and RpoC which comprise proteins involved in DNA and RNA synthesis. A majority of these proteins lack sequence homology with proteins of known function and are currently annotated as proteins of unknown function. The unique amino acid compositions of these proteins, their limited capacity to tolerate mutations, and their apparent exclusivity to M. abscessus suggest that they play essential roles in the pathogens ability to establish and maintain infection in humans. These findings highlight potentially promising targets for future drug development aimed at combating M. abscessus infections.