Pleiotropic role of PAX cyclolipopeptides in the Xenorhabdus bacterium mutualistically associated with entomopathogenic nematodes

Xenorhabdusis an entomopathogenic bacterium involved in a mutualistic relationship withSteinernemanematodes.Xenorhabdusproduces a multitude of specialized metabolites by Non-Ribosomal Peptide Synthetases (NRPSs) pathways to mediate bacterial–nematode– insect interactions. PAX cyclolipopeptides are a family of NRP-type molecules whose ecological role remains poorly understood. In this study, the pleiotropic role of PAX peptides in the life cycle ofXenorhabdus nematophilahas been investigated. By mass spectrometry analysis, we first demonstrated that PAX peptides were detected from the pathogenic stage up to the necrotrophic stage. We discovered that the bromothymol blue adsorption phenotype historically used to discriminateXenorhabdusvariants was associated with the presence of PAX peptides. We found that PAX peptides were positively involved in biofilm formation and negatively involved in swimming motility. PAX peptides were also shown to promotein vivothe production of infectiveSteinernemajuveniles, suggesting their involvement in the mutualistic relationship betweenXenorhabdusand its nematode partner. Finally, we showed that thepaxTABCcluster as well as PAX peptide production was conserved across the wholeXenorhabdusgenus except inXenorhabdus poinariiandXenorhabdus ishibashii. This work has revealed multiple new ecological roles for NRP-type peptides.