Host-pathogen Coadaptation by running with PAR protein

SummaryHost-pathogen coadaptation is mutually beneficial for the survival of both organisms. Embryo development is a crucial aspect of animal evolution as it ensures the continuation of their offspring. However, there is little understanding of the coadaptation mechanisms underlying embryo developmental factors in host-pathogen interactions. Here, by using aC. elegans-P. aeruginosainfection model, we demonstrate that PAR-5, essential for the establishment of anterior-posterior polarity within the single cellC. eleganszygote, acts as a mediator in regulating host-pathogen co-evolution. We discover thatPseudomonas aeruginosa-PA14 infection induces PAR-5 expression, which accelerates animal embryo development and ensures the continuity of their offspring. Moreover, PA14 stimulates host PAR-5 secretion, which reduces the virulence of PA14. Both functions of PAR-5 are beneficial for host survival. Meanwhile, pathogens utilize PAR-5 to inhibit host immunity/UPRERby bypassing the core PMK-1-mediated innate immunity and activating mTOR by interacting with LET-363, promoting pathogen spread. Therefore, our study uncovers an unexpected mechanism in host-pathogen co-evolution that targets a host embryo developmental factor, promoting coexistence and facilitating the adaptation of both hosts and pathogens.