title: Boric acid destabilizes the hyphal cytoskeleton and inhibits invasive growth of Candida albicans.
abstract: Exposure of Candida albicans to sub-lethal concentrations of boric acid (BA) restricts the dimorphic fungus to its yeast morphology and prevents the formation of invasive hyphae on solid substrates. Exposure to BA causes a rapid and reversible disappearance of polarisome and Spitzenkörper in growing hyphae. In BA-treated hyphae of C. albicans, actin quickly reorganizes from cytoplasmic cables to cortical patches and cell wall growth switches from an apical to an isotropic pattern. As a result of the cytoskeletal changes, the hyphal tips broaden and directional growth of hyphae ceases in the presence of BA. An analysis of homozygous deletion strains showed that mutants with constitutive or enhanced hyphal growth (tup1, nrg1, ssn6, rbf1) are BA-sensitive, demonstrating that cellular morphology is a major determinant of BA tolerance. The screening of deletion mutants also showed that deficiencies of the main activator of hyphal gene expression, Efg1, and the Rim101-signalling cascade, leading to Efg1 activation, cause BA resistance. Taken together, the data presented show that the selective inhibitory effect on BA on C. albicans hyphae is rooted in a disruption of apical cytoskeletal elements of growing hyphae.
authors.affiliation: Department of Biochemistry and Nutrition, Des Moines University, IA, USA.
authors.forename: Benjamin R
authors.initials: BR
authors.lastname: Pointer
authors.forename: Michael P
authors.initials: MP
authors.lastname: Boyer
authors.forename: Martin
authors.initials: M
authors.lastname: Schmidt
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology*; D001888:Boric Acids / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D003599:Cytoskeleton / Q000187:drug effects* / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects; D025301:Hyphae / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism
chemical_list: D000935:Antifungal Agents; D001888:Boric Acids; D005656:Fungal Proteins; C032688:boric acid
keywords: Candida albicans; Efg1; Tup1; boric acid; yeast-to-hyphae transition