title: Candida albicans-conditioned medium protects yeast cells from oxidative stress: a possible link between quorum sensing and oxidative stress resistance.
abstract: Candida albicans, the most frequent fungal pathogen of humans, encounters high levels of oxidants following ingestion by professional phagocytes and through contact with hydrogen peroxide-producing bacteria. In this study, we provide evidence that C. albicans is able to coordinately regulate the oxidative stress response at the global cell population level by releasing protective molecules into the surrounding medium. We demonstrate that conditioned medium, which is defined as a filter-sterilized supernatant from a C. albicans stationary-phase culture, is able to protect yeast cells from both hydrogen peroxide and superoxide anion-generating agents. Exponential-phase yeast cells preexposed to conditioned medium were able to survive levels of oxidative stress that would normally kill actively growing yeast cells. Heat treatment, digestion with proteinase K, pH adjustment, or the addition of the oxidant scavenger alpha-tocopherol did not alter the ability of conditioned medium to induce a protective response. Farnesol, a heat-stable quorum-sensing molecule (QSM) that is insensitive to proteolytic enzymes and is unaffected by pH extremes, is partly responsible for this protective response. In contrast, the QSM tyrosol did not alter the sensitivity of C. albicans cells to oxidants. Relative reverse transcription-PCR analysis indicates that Candida-conditioned growth medium induces the expression of CAT1, SOD1, SOD2, and SOD4, suggesting that protection may be mediated through the transcriptional regulation of antioxidant-encoding genes. Together, these data suggest a link between the quorum-sensing molecule farnesol and the oxidative stress response in C. albicans.
authors.affiliation: Center for Oral Health Research, Department of Stomatology, Medical University of South Carolina, Charleston, USA. westwatc@musc.edu
authors.forename: Caroline
authors.initials: C
authors.lastname: Westwater
authors.forename: Edward
authors.initials: E
authors.lastname: Balish
authors.forename: David A
authors.initials: DA
authors.lastname: Schofield
mesh_terms: D000925:Anticoagulants / Q000494:pharmacology; D000933:Antifibrinolytic Agents / Q000494:pharmacology; D000975:Antioxidants / Q000737:chemistry / Q000378:metabolism*; D002176:Candida albicans / Q000187:drug effects / Q000502:physiology*; D017077:Culture Media, Conditioned / Q000737:chemistry* / Q000378:metabolism; D000431:Ethanol / Q000378:metabolism; D005204:Farnesol / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D009285:Naphthoquinones / Q000494:pharmacology; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress; D024483:Vitamin K 3 / Q000494:pharmacology; D024502:alpha-Tocopherol / Q000378:metabolism
chemical_list: D000925:Anticoagulants; D000933:Antifibrinolytic Agents; D000975:Antioxidants; D017077:Culture Media, Conditioned; D005656:Fungal Proteins; D009285:Naphthoquinones; D016877:Oxidants; D000431:Ethanol; D005204:Farnesol; D024483:Vitamin K 3; D006861:Hydrogen Peroxide; D024502:alpha-Tocopherol; C014758:plumbagin