Article Dans Une Revue Nature Communications Année : 2025

A glycosylated lipooctapeptide promotes uptake and growth of Mycobacterium abscessus in the host

Mélanie Cortes
Nicolas Durand
Franck Biet

Résumé

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.

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hal-05034871 , version 1 (27-05-2025)

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Louis David Leclercq, Vincent Le Moigne, Wassim Daher, Mélanie Cortes, Bertus Viljoen, et al.. A glycosylated lipooctapeptide promotes uptake and growth of Mycobacterium abscessus in the host. Nature Communications, 2025, 16 (1), pp.3326. ⟨10.1038/s41467-025-58455-5⟩. ⟨hal-05034871⟩
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