Identification of a muropeptide precursor transporter from gut microbiota and its role in preventing intestinal inflammation

authors

• Liuu Sophie
• Nepelska Malgorzata
• Pfister Hélène
• Gamelas Magalhaes Joao
• Chevalier Gregoire
• Strozzi Francesco
• Billerey Coline
• Maresca Marc
• Nicoletti Cendrine
• Di Pasquale Eric
• Pechard Charlie
• Bardouillet Laureen
• Girardin Stephen
• Boneca Ivo Gomperts
• Doré Joel
• Blottière Hervé
• Bonny Christophe
• Chene Laurent
• Cultrone Antonietta

keywords

• ABC-transporter
• Inflammation
• Microbiota
• Muropeptide precursor

document type

abstract

The gut microbiota is a considerable source of biologically active compounds that can promote intestinal homeostasis and improve immune responses. Here, we used large expression libraries of cloned metagenomic DNA to identify compounds able to sustain an anti-inflammatory reaction on host cells. Starting with a screen for NF-κB activation, we have identified overlapping clones harbouring a heterodimeric ATP-binding cassette (ABC)-transporter from a Firmicutes. Extensive purification of the clone’s supernatant demonstrates that the ABC-transporter allows for the efficient extracellular accumulation of three muropeptide precursor, with anti-inflammatory properties. They induce IL-10 secretion from human monocyte-derived dendritic cells and proved effective in reducing AIEC LF82 epithelial damage and IL-8 secretion in human intestinal resections. In addition, treatment with supernatants containing the muropeptide precursor reduces body weight loss and improves histological parameters in Dextran Sulfate Sodium (DSS)-treated mice. Until now, the source of peptidoglycan fragments was shown to come from the natural turnover of the peptidoglycan layer by endogenous peptidoglycan hydrolases. This is a report showing an ABC-transporter as a natural source of secreted muropeptide precursor and as an indirect player in epithelial barrier strengthening. The mechanism described here might represent an important component of the host immune homeostasis.

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