A symbiont-derived biosurfactant couples bacterial surface properties to host-mediated clearance

Host mechanisms that regulate intestinal colonization are viewed as acting on microbes, yet microbial traits that determine susceptibility to host control remain poorly understood. Using the association between Caenorhabditis elegans and its symbiont Pseudomonas lurida MYb11, we identify the cyclic lipopeptide biosurfactant massetolide as a bacterial factor that couples microbial physiology to host-mediated clearance. An unbiased screen of >11,000 bacterial mutants coupled to a host transcriptional reporter, combined with bacterial and host genetics, chemical complementation, transcriptomics, and physiological analyses, revealed that massetolide triggers host TGF-β and serotonergic signaling to promote intestinal peristalsis, limiting colonization. Massetolide also alters bacterial surface properties and promotes swarming. Experimentally increased serotonin-dependent peristalsis selectively reduces colonization by massetolide-producing bacteria, whereas massetolide-deficient bacteria remain resistant to host-mediated expulsion. Together, our findings reveal a symbiont-derived biosurfactant that links host neuroimmune control of intestinal peristalsis with bacterial susceptibility to expulsion, coupling host and microbial physiology to regulate symbiont abundance.