Commensal Yeast PromotesSalmonellaTyphimurium Virulence

Abstract

AbstractEnteric pathogens engage in complex interactions with the host and the resident microbiota to establish gut colonization. Although mechanistic interactions between enteric pathogens and bacterial commensals have been extensively studied, whether and how commensal fungi affect pathogenesis of enteric infections remains largely unknown. Here we show that colonization with the common human gut commensal fungusCandida albicansworsened infections with the enteric pathogenSalmonella entericaserovar Typhimurium. Presence ofC. albicansin the mouse gut increasedSalmonellacecum colonization and systemic dissemination. We investigated the underlying mechanism and found thatSalmonellabinds toC. albicansvia Type 1 fimbriae and uses its Type 3 Secretion System (T3SS) to deliver effector proteins intoC. albicans. A specific effector, SopB, was sufficient to manipulateC. albicansmetabolism, triggering increased arginine biosynthesis inC. albicansand the release of millimolar amounts of arginine into the extracellular environment. The released arginine, in turn, induced T3SS expression inSalmonella, increasing its invasion of epithelial cells.C. albicansdeficient in arginine production was unable to increaseSalmonellavirulencein vitroorin vivo. In addition to modulating pathogen invasion, arginine also directly influenced the host response to infection. Arginine-producingC. albicansdampened the inflammatory response duringSalmonellainfection, whereasC. albicansdeficient in arginine production did not. Arginine supplementation in the absence ofC. albicansincreased the systemic spread ofSalmonellaand decreased the inflammatory response, phenocopying the presence ofC. albicans. In summary, we identifiedC. albicanscolonization as a susceptibility factor for disseminatedSalmonellainfection, and arginine as a central metabolite in the cross-kingdom interaction between fungi, bacteria, and host.