Lipoarabinomannan modification as a source of phenotypic heterogeneity in host-adapted Mycobacterium abscessus isolates

• DOI: 10.1073/pnas.2403206121
• Publication Date: 2024-04-17T17:42:02Z
• Authors: Kavita De; Juan M. Belardinelli; Arun Prasad Pandu...; Teddy Ehianeta; Elena Lian; Zuzana Palčeková; Ha Lam; Mercedes Gonzalez...; Josephine M. Bryant; Tom L. Blundell; Julian Parkhill; R. Andres Floto; Todd L. Lowary; William H. Wheat; Mary Jackson
• Keywords: Mycobacterium abscessus; Nonsynonymous substitution; Lipoarabinomannan

Mycobacterium abscessus is increasingly recognized as the causative agent of chronic pulmonary infections in humans. One genes found to be under strong evolutionary pressure during adaptation M. human lung embC which encodes an arabinosyltransferase required for biosynthesis cell envelope lipoglycan, lipoarabinomannan (LAM). To assess impact patient-derived mutations on physiology and virulence , were introduced isogenic background ATCC 19977 resulting strains probed phenotypic changes a variety vitro host cell-based assays relevant infection. We show that mutational variations EmbC result unexpectedly large number abscessus, its interactions with innate immune cells. Not only did mutants produce previously unknown forms LAM truncated arabinan domain 3-linked oligomannoside chains, they also displayed significantly altered cording, sliding motility, biofilm-forming capacities. The further differed from wild-type their ability replicate induce inflammatory responses monocyte–derived macrophages epithelial fact different associated distinct physiologic pathogenic outcomes indicates structural alterations caused by nonsynonymous nucleotide polymorphisms may rapid, one-step, way generate broad-spectrum diversity beneficial survival within heterogeneous constantly evolving environment infected airway.