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<p>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. <i>Mycobacterium abscessus</i>, an emerging rapid-growing pathogen, transitions from a smooth to a virulent rough variant upon the loss of surface GPL. Here, we discovered that <i>M. abscessus</i> and phylogenetically-close species harbor a second GPL-related locus, comprising two adjacent non-ribosomal peptide synthetase genes, <i>MAB_4690c</i> and <i>MAB_4691c</i>. A <i>MAB_4690c</i> deletion mutant (Δ<i>MAB_4690c</i>) failed to produce a yet undescribed lipid, designated GL8P for glycosylated lipooctapeptide, sharing an acylated octapeptide core adorned by mono or di-<i>O</i>-rhamnosyl substituents. Δ<i>MAB_4690c</i> 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 <i>M. abscessus</i>. These results highlight the role of GL8P in the pathophysiology of infection by rough <i>M</i>. <i>abscessus</i> and suggest its potential as a selective marker for <i>M</i>. <i>abscessus</i> infections.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年4月8日

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  • Louis David Leclercq,
  • Vincent Le Moigne,
  • Wassim Daher,
  • Mélanie Cortes,
  • Bertus Viljoen,
  • Yara Tasrini,
  • Xavier Trivelli,
  • Hélène Lavanant,
  • Isabelle Schmitz-Afonso,
  • Nicolas Durand,
  • Franck Biet,
  • Yann Guérardel,
  • Laurent Kremer,
  • Jean-Louis Herrmann

摘要

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.