Abstract
Pathogenic mycobacteria produce a wide array of lipids which participate in host cell interactions and virulence. While some of these are conserved across all mycobacteria, others, like glycopeptidolipids (GPL), are restricted to a few species. Mycobacterium abscessus , an emerging rapid-growing pathogen, transitions from a smooth to a virulent rough variant upon the loss of surface GPL. Here, we discovered that M. abscessus and phylogenetically-close species harbor a second GPL-related locus, comprising two adjacent non-ribosomal peptide synthetase genes, MAB_4690c and MAB_4691c . A MAB_4690c deletion mutant (Δ MAB_4690c ) failed to produce a yet undescribed lipid, designated GL8P for glycosylated lipooctapeptide, sharing an acylated octapeptide core adorned by mono or di- O -rhamnosyl substituents. Δ MAB_4690c exhibited impaired uptake and survival in THP-1 cells and was attenuated in mice. Importantly, GL8P elicited a strong humoral response in patients infected with M. abscessus . These results highlight the role of GL8P in the pathophysiology of infection by rough M . abscessus and suggest its potential as a selective marker for M . abscessus infections.