Phage resistance mutations affecting the bacterial cell surface increase susceptibility to fungi in a model cheese community.

Diverse populations of bacteriophages infect and coevolve with their bacterial hosts. Although host recognition and infection occur within microbiomes, the molecular mechanisms underlying host-phage interactions within a community context remain poorly studied. The biofilms (rinds) of aged cheeses contain taxonomically diverse microbial communities that follow reproducible growth patterns and can be manipulated under laboratory conditions. In this study, we use cheese as a model for studying phage-microbe interactions by identifying and characterizing a tractable host-phage pair co-occurring within a model Brie-like community. We isolated a novel bacteriophage, TS33, that kills sp. JB232, a member of the model community. TS33 is easily propagated in the lab and naturally co-occurs in the cheese community, rendering it a prime candidate for the study of host-phage interactions. We performed growth assays of the , TS33, and the fungal community members, and . Employing Random Barcode Transposon Sequencing experiments, we identified candidate host factors that contribute to TS33 infectivity, many of which are homologs of bacterial O-antigen genes. mutants in these genes exhibit decreased susceptibility to phage infection, but experience negative fitness effects in the presence of the fungi. Therefore, mutations in O-antigen biosynthesis homologs may have antagonistic pleiotropic effects in that have major consequences for its interactions with the rest of the community. Ongoing and future studies aim to unearth the molecular mechanisms by which the O-antigen of mediates its interactions with its viral and fungal partners.