title: Regulation of Candida albicans morphogenesis by fatty acid metabolites.
abstract: Candida albicans is an opportunistic dimorphic fungus that inhabits various host mucosal sites. Conversion from the yeast to the hyphal form has been associated with increased virulence and mucosal invasiveness. C. albicans morphogenesis is regulated by multiple signals and signaling pathways. However, signals that control morphogenesis in vivo are unknown. We investigated the effects of host long chain fatty acids, eicosanoids, and bacterial short chain fatty acids on control of germination. None of the C18 or C20 fatty acids tested had an effect on enhancing germ tube formation (arachidonic acid, oleic acid, linolenic acid, or gamma-linolenic acid). Among the different eicosanoids, both prostaglandin E2 and thromboxane B2 significantly enhanced serum-induced germination by C. albicans. Addition of antiprostaglandin or antithromboxane antibodies to serum alone inhibited germ tube formation by almost 30%, while control antibody had no effect, indicating that these eicosanoids are major morphogenic factors in the serum. Since these molecules also bind to albumin, this may also explain the hyphal transforming activity in serum that associates with albumin. Interestingly, short chain fatty acids (butyric acid), the product of lactic acid bacteria (LAB), inhibited germination. In addition, LAB culture supernatants as well as live LAB also inhibited C. albicans morphogenesis. Overall, these results indicate that fatty acid metabolites and fatty acid pathways can up-regulate and down-regulate germination in C. albicans.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor 48109-0642, USA.
authors.forename: Mairi C
authors.initials: MC
authors.lastname: Noverr
authors.forename: Gary B
authors.initials: GB
authors.lastname: Huffnagle
mesh_terms: D002176:Candida albicans / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development*; D003470:Culture Media / Q000737:chemistry; D015232:Dinoprostone / Q000494:pharmacology; D005227:Fatty Acids / Q000378:metabolism* / Q000494:pharmacology*; D015966:Gene Expression Regulation, Fungal; D009024:Morphogenesis; D013929:Thromboxane B2 / Q000494:pharmacology
chemical_list: D003470:Culture Media; D005227:Fatty Acids; D013929:Thromboxane B2; D015232:Dinoprostone