title: Interspecies Interactions betweenClostridium difficileandCandida albicans.
abstract: The facultative anaerobic polymorphic fungusCandida albicansand the strictly anaerobic Gram-positive bacteriumClostridium difficileare two opportunistic pathogens residing in the human gut. While a few studies have focused on the prevalence ofC. albicansinC. difficile-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 betweenC. albicansandC. difficilewere investigated. In the presence ofC. albicans,C. difficilewas able to grow under aerobic, normally toxic, conditions. This phenomenon was neither linked to adherence of bacteria to hyphae nor to biofilm formation byC. albicans. Conditioned medium ofC. difficileinhibited hyphal growth ofC. albicans, which is an important virulence factor of the fungus. In addition, it induced hypha-to-yeast conversion.p-Cresol, a fermentation product of tyrosine produced byC. difficile, also induced morphological effects and was identified as an active component of the conditioned medium. This study shows that in the presence ofC. albicans,C. difficilecan persist and grow under aerobic conditions. Furthermore,p-cresol, produced byC. difficile, is involved in inhibiting hypha formation ofC. albicans, directly affecting the biofilm formation and virulence ofC. albicans. This study is the first detailed characterization of the interactions between these two gut pathogens.IMPORTANCECandida albicansandClostridium difficileare two opportunistic pathogens that reside in the human gut. A few studies have focused on the prevalence ofC. albicansinC. difficile-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 ofC. albicans,C. difficilecan survive under ambient aerobic conditions, which would otherwise be toxic. We also found thatC. difficileaffects the hypha formation ofC. albicans, most likely through the excretion ofp-cresol. This ultimately leads to an inability ofC. albicansto form a biofilm. Our study provides new insights into interactions betweenC. albicansandC. difficileand bears relevance to both fungal and bacterial disease.
authors.affiliation: Department of Preventive Dentistry, Academic Centre for Dentistry Amsterdam (ACTA), Free University of Amsterdam and the University of Amsterdam, Amsterdam, The Netherlands; Department of Medical Microbiology, Leiden University Medical Center (LUMC), Leiden, The Netherlands.
authors.forename: Pim T
authors.initials: PT
authors.lastname: van Leeuwen
authors.affiliation: Department of Preventive Dentistry, Academic Centre for Dentistry Amsterdam (ACTA), Free University of Amsterdam and the University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Jasper M
authors.initials: JM
authors.lastname: van der Peet
authors.affiliation: Department of Oral Biochemistry, Academic Centre for Dentistry Amsterdam (ACTA), Free University of Amsterdam and the University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Floris J
authors.initials: FJ
authors.lastname: Bikker
authors.affiliation: Department of Preventive Dentistry, Academic Centre for Dentistry Amsterdam (ACTA), Free University of Amsterdam and the University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Michel A
authors.initials: MA
authors.lastname: Hoogenkamp
authors.affiliation: Department of Medical Microbiology, Leiden University Medical Center (LUMC), Leiden, The Netherlands.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Oliveira Paiva
authors.affiliation: Center for Proteomics and Metabolomics, Leiden University Medical Center (LUMC), Leiden, The Netherlands.
authors.forename: Sarantos
authors.initials: S
authors.lastname: Kostidis
authors.affiliation: Center for Proteomics and Metabolomics, Leiden University Medical Center (LUMC), Leiden, The Netherlands.
authors.forename: Oleg A
authors.initials: OA
authors.lastname: Mayboroda
authors.affiliation: Department of Medical Microbiology, Leiden University Medical Center (LUMC), Leiden, The Netherlands.
authors.forename: Wiep Klaas
authors.initials: WK
authors.lastname: Smits
authors.affiliation: Department of Preventive Dentistry, Academic Centre for Dentistry Amsterdam (ACTA), Free University of Amsterdam and the University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Bastiaan P
authors.initials: BP
authors.lastname: Krom
keywords: Candida albicans; Clostridium difficile; interspecies interactions