Enterococcus faecalis Inhibits Hyphal Morphogenesis and Virulence of Candida albicans

Abstract

The Gram-positive bacteriumEnterococcus faecalisand the fungusCandida albicansare both found as commensals in many of the same niches of the human body, such as the oral cavity and gastrointestinal (GI) tract. However, both are opportunistic pathogens and have frequently been found to be coconstituents of polymicrobial infections. Despite these features in common, there has been little investigation into whether these microbes affect one another in a biologically significant manner. Using aCaenorhabditis elegansmodel of polymicrobial infection, we discovered thatE. faecalisandC. albicansnegatively impact each other's virulence. Much of the negative effect ofE. faecalisonC. albicanswas due to the inhibition ofC. albicanshyphal morphogenesis, a developmental program crucial toC. albicanspathogenicity. We discovered that the inhibition was partially dependent on the Fsr quorum-sensing system, a major regulator of virulence inE. faecalis. Specifically, two proteases regulated by Fsr, GelE and SerE, were partially required. Further characterization of the inhibitory signal revealed that it is secreted into the supernatant, is heat resistant, and is between 3 and 10 kDa. The substance was also shown to inhibitC. albicansfilamentation in the context of anin vitrobiofilm. Finally, a screen of anE. faecalistransposon mutant library identified other genes required for suppression ofC. albicanshyphal formation. Overall, we demonstrate a biologically relevant interaction between two clinically important microbes that could affect treatment strategies as well as impact our understanding of interkingdom signaling and sensing in the human-associated microbiome.