A glycosylated lipooctapeptide promotes uptake and growth of Mycobacterium abscessus in the host
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 (ΔMAB_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. ΔMAB_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.
Authors
- Franck Biet (ORCID: https://orcid.org/0000-0001-8425-6158)
- Hélène Lavanant (ORCID: https://orcid.org/0000-0002-2963-0327)
- Wassim Daher (ORCID: https://orcid.org/0000-0001-9026-5333)
- Yara Tasrini
- Yann Guérardel (ORCID: https://orcid.org/0000-0003-4967-9512)
- Isabelle Schmitz‐Afonso (ORCID: https://orcid.org/0000-0003-0665-0074)
- Mélanie Cortès (ORCID: https://orcid.org/0009-0000-0059-5356)
- Jean‐Louis Herrmann (ORCID: https://orcid.org/0000-0003-2347-6418)
- Nicolas Durand (ORCID: https://orcid.org/0000-0002-3613-2609)
- Laurent Kremer (ORCID: https://orcid.org/0000-0002-6604-4458)
- Xavier Trivelli (ORCID: https://orcid.org/0000-0001-6775-9650)
- Louis-David Leclercq (ORCID: https://orcid.org/0000-0002-2513-7295)
- B.C. Viljoen
- Vincent Le Moigne (ORCID: https://orcid.org/0000-0003-2012-1750)
Institutions
- Université de Tours (FR)
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- Université de Versailles Saint-Quentin-en-Yvelines (FR)
- Université de Montpellier (FR)
- Université de Lille (FR)
- Université Paris-Saclay (FR)
- Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement (FR)
- Assistance Publique – Hôpitaux de Paris (FR)
- Institut de Pharmacologie et de Biologie Structurale (FR)
- Normandie Université (FR)
- Physiologie de la Reproduction et des Comportements (FR)
- Unité de Glycobiologie Structurale et Fonctionnelle (FR)
- Biologie des oiseaux et aviculture (FR)
- Services déconcentrés d'appui à la recherche Val de Loire (FR)
- Hôpital Raymond-Poincaré (FR)
- Institut de Recherche en Infectiologie de Montpellier (FR)
- Gifu University (JP)
- Université d'Artois (FR)
- Université de Rouen Normandie (FR)
- École Centrale de Lille (FR)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-04-08
- DOI
- https://doi.org/10.1038/s41467-025-58455-5
- Citations
- 4
- Primary Topic
- Mycobacterium research and diagnosis
- Type
- article
- Field-Weighted Citation Impact
- 5.42
Funders
- Agence Nationale de la Recherche
- Institut National de la Santé et de la Recherche Médicale
- Fondation pour la Recherche Médicale
- Association Vaincre la Mucoviscidose
- Université de Versailles Saint-Quentin-en-Yvelines