Interspecies Interactions between Clostridium difficile and Candida albicans

Abstract

The facultative anaerobic polymorphic fungus <i>Candida albicans</i> and the strictly anaerobic Gram-positive bacterium <i>Clostridium difficile</i> are two opportunistic pathogens residing in the human gut. While a few studies have focused on the prevalence of <i>C. albicans</i> in <i>C. difficile</i>-infected patients, the nature of the interactions between these two microbes has not been studied thus far. In the current study, both chemical and physical interactions between <i>C. albicans</i> and <i>C. difficile</i> were investigated. In the presence of <i>C. albicans</i>, <i>C. difficile</i> was able to grow under aerobic, normally toxic, conditions. This phenomenon was neither linked to adherence of bacteria to hyphae nor to biofilm formation by <i>C. albicans</i>. Conditioned medium of <i>C. difficile</i> inhibited hyphal growth of <i>C. albicans</i>, which is an important virulence factor of the fungus. In addition, it induced hypha-to-yeast conversion. <i>p</i>-Cresol, a fermentation product of tyrosine produced by <i>C. difficile</i>, also induced morphological effects and was identified as an active component of the conditioned medium. This study shows that in the presence of <i>C. albicans</i>, <i>C. difficile</i> can persist and grow under aerobic conditions. Furthermore, <i>p</i>-cresol, produced by <i>C. difficile</i>, is involved in inhibiting hypha formation of <i>C. albicans</i>, directly affecting the biofilm formation and virulence of <i>C. albicans</i>. This study is the first detailed characterization of the interactions between these two gut pathogens. <b>IMPORTANCE</b><i>Candida albicans</i> and <i>Clostridium difficile</i> are two opportunistic pathogens that reside in the human gut. A few studies have focused on the prevalence of <i>C. albicans</i> in <i>C. difficile</i>-infected patients, but none have shown the interaction(s) that these two organisms may or may not have with each other. In this study, we used a wide range of different techniques to better understand this interaction at a macroscopic and microscopic level. We found that in the presence of <i>C. albicans</i>, <i>C. difficile</i> can survive under ambient aerobic conditions, which would otherwise be toxic. We also found that <i>C. difficile</i> affects the hypha formation of <i>C. albicans</i>, most likely through the excretion of <i>p</i>-cresol. This ultimately leads to an inability of <i>C. albicans</i> to form a biofilm. Our study provides new insights into interactions between <i>C. albicans</i> and <i>C. difficile</i> and bears relevance to both fungal and bacterial disease.