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bioRxiv · 10.64898/2025.12.15.694388

Symbiosis through lysis: prophage activation underlies Lactiplantibacillus plantarum probiotic function

Zhu, C.·Manuse, S.·Perrier, Q.·Akherraz, H.·Ramos, C. I.·Zhang, M.·Grangeasse, C.·Leulier, F.·Matos, R. C.
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Abstract

The release of bacterial bioactive molecules across the gut barrier is a crucial yet poorly understood step in microbe-host molecular dialog. Here we unravel a phage-driven mechanism that enables this process in a symbiont that supports host adaptive growth. In Lactiplantibacillus plantarum NC8 (LpNC8), we identify a stress-inducible prophage, pp2, that undergoes genotoxic-stress-dependent activation in vivo and triggers holin-lysin-mediated lysis. This controlled lytic program produces phage particles together with extracellular vesicles (EVs), enriched in symbiotic cues, including lipoteichoic acids. In a model of beneficial symbiosis, pp2-dependent lysis is strictly required for the ability of LpNC8to support juvenile growth in nutritionally challenged Drosophila melanogaster. Disruption of pp2-dependent lysis abolishes EVs release in vitro and alters the growth-promoting effect in vivo. We show that the acidic region of the Drosophila midgut, but not host antimicrobial peptides nor lysozymes, acts as a physiological trigger of prophage induction: removal of this acidic compartment markedly reduces phage production and impairs LpNC8-mediated growth promotion. These findings demonstrate that host gut physiology regulates prophage activation and reveal prophage-induced lysis as a previously unrecognized mechanism by which a beneficial gut bacterium releases symbiotic cues to support host development during nutritional stress.

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Zhu, C., Manuse, S., Perrier, Q., Akherraz, H., Ramos, C. I., Zhang, M., Grangeasse, C., Leulier, F., Matos, R. C.. 2025-12-15. Symbiosis through lysis: prophage activation underlies Lactiplantibacillus plantarum probiotic function. https://doi.org/10.64898/2025.12.15.694388

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