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 pathogens utilizing the and bacterium model system. First, we find that larvae efficiently outcompete and typically drive a bacterial switch from pathogenicity to commensalism toward the fly. Furthermore, larvae reshape the transcriptomic and metabolic profiles of characterized by a lifestyle switch. More importantly, the host alters pathogenicity and heterogeneity of in the single-cell resolution. Finally, we find that larvae-derived AMPs are required to recapitulate the response of to 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.