Hosts Manipulate Lifestyle Switch and Pathogenicity Heterogeneity of Opportunistic Pathogens in the Single-cell Resolution

Host-microbe interactions are virtually bidirectional, but how the host affects their microbiome is poorly understood. Here, we report that the host is a critical modulator to regulate the lifestyle switch and pathogenicity heterogeneity of the opportunistic pathogensSerratia marcescensutilizing theDrosophilaand bacterium model system. First, we find thatDrosophilalarvae efficiently outcompeteS. marcescensand typically drive a bacterial switch from pathogenicity to commensalism toward the fly. Furthermore,Drosophilalarvae reshape the transcriptomic and metabolic profiles ofS. marcescenscharacterized by a lifestyle switch. More important, the host alters pathogenicity and heterogeneity ofS. marcescensin the single-cell resolution. Finally, we find that larvae-derived AMPs are required to recapitulate the response ofS. marcescensto larvae. Altogether, our findings provide an insight into the pivotal roles of the host in harnessing the life history and heterogeneity of symbiotic bacterial cells, advancing knowledge of the reciprocal relationships between the host and pathogen.