title: Resistance to echinocandins comes at a cost: the impact of FKS1 hotspot mutations on Candida albicans fitness and virulence.
abstract: The emergence of Candida strains carrying FKS1 hotspot mutations associated with resistance to echinocandins is cause for concern. However, to assess the potential of such strains to spread within the community and cause lethal infection, the impact of FKS1 mutations on Candida fitness must be determined. We present evidence that C. albicans fks1 mutations carry significant fitness and virulence costs, which are associated with the production of a thickened, chitin-rich cell wall, impaired filamentation and induction of a dampened inflammatory response. If these phenotypic changes remain stable, they can serve as a basis for rational design of strategies to control the spread of echinocandin resistance.
authors.affiliation: Infectious Diseases Unit, Tel Aviv Medical Center and Sackler School of Medicine, Tel Aviv, Israel. ronenba@tasmc.health.gov.il
authors.forename: Ronen
authors.initials: R
authors.lastname: Ben-Ami
authors.forename: Dimitrios P
authors.initials: DP
authors.lastname: Kontoyiannis
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics / Q000472:pathogenicity*; D002177:Candidiasis / Q000382:microbiology*; D025141:Drug Resistance, Fungal; D054714:Echinocandins / Q000494:pharmacology*; D005656:Fungal Proteins / Q000235:genetics* / Q000378:metabolism; D005964:Glucosyltransferases / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D009154:Mutation; D014774:Virulence / Q000187:drug effects
chemical_list: D000935:Antifungal Agents; D054714:Echinocandins; D005656:Fungal Proteins; D005964:Glucosyltransferases