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bioRxiv · 10.1101/2025.04.11.648461

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

Claveyroles, N.·Lanois-Nouri, A.·El Fannassi, I.·Ogier, J.-c.·Pages, S.·Chouchou, A.·Cazals, G.·Valette, G.·Carre-Mlouka, A.·Givaudan, A.
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Abstract

Xenorhabdus is an entomopathogenic bacterium involved in a mutualistic relationship with Steinernema nematodes. Xenorhabdus produces 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 of Xenorhabdus nematophila has 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 discriminate Xenorhabdus variants 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 promote in vivo the production of infective Steinernema juveniles, suggesting their involvement in the mutualistic relationship between Xenorhabdus and its nematode partner. Finally, we showed that the paxTABC cluster as well as PAX peptide production was conserved across the whole Xenorhabdus genus except in Xenorhabdus poinarii and Xenorhabdus ishibashii. This work has revealed multiple new ecological roles for NRP-type peptides. ImportanceXenorhabdus bacteria are models of particular interest for their mutualistic relationship with Steinernema nematodes and their ability to produce a wide range of natural NRP-type bioactive metabolites. These compounds are mostly studied for their medical or industrial applications, but their ecological role is poorly understood. This study provides a dynamic characterization of PAX cyclolipopeptide presence during Xenorhabdus nematophila life cycle, as well as confirmation of their production by 7 different strains within the Xenorhabdus genus. We revealed new multiple functions for PAX peptides in biofilm formation, swimming motility and juvenile nematode production. A deeper understanding of how PAX peptides interact with the nematode host would provide a better insight into the role of these cyclolipopeptides in bacterial-nematode mutualism.

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Claveyroles, N., Lanois-Nouri, A., El Fannassi, I., Ogier, J.-c., Pages, S., Chouchou, A., Cazals, G., Valette, G., Carre-Mlouka, A., Givaudan, A.. 2025-04-14. Pleiotropic role of PAX cyclolipopeptides in the Xenorhabdus bacterium mutualistically associated with entomopathogenic nematodes. https://doi.org/10.1101/2025.04.11.648461

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