title: A histone deacetylase complex mediates biofilm dispersal and drug resistance in Candida albicans.
abstract: Biofilms are resilient, surface-associated communities of cells with specialized properties (e.g., resistance to drugs and mechanical forces) that are distinct from those of suspension (planktonic) cultures. Biofilm formation by the opportunistic human fungal pathogen Candida albicans is medically relevant because C. albicans infections are highly correlated with implanted medical devices, which provide efficient substrates for biofilm formation; moreover, biofilms are inherently resistant to antifungal drugs. Biofilms are also important for C. albicans to colonize diverse niches of the human host. Here, we describe four core members of a conserved histone deacetylase complex in C. albicans (Set3, Hos2, Snt1, and Sif2) and explore the effects of their mutation on biofilm formation. We find that these histone deacetylase complex members are needed for proper biofilm formation, including dispersal of cells from biofilms and multifactorial drug resistance. Our results underscore the importance of the physical properties of biofilms in contributing to drug resistance and dispersal and lay a foundation for new strategies to target biofilm dispersal as a potential antifungal intervention.
  
  
  OBJECTIVE
  Through the formation of biofilms--surface-associated communities of cells--microorganisms can establish infections, become drug resistant, and evade the host immune system. Here we investigate how four core members of a conserved histone deacetylase complex mediate biofilm formation by Candida albicans, the major fungal pathogen of humans. We show that this histone deacetylase complex is required for biofilm dispersal, a process through which cells leave the biofilm to establish new infections. We also show that the deacetylase complex mediates biofilm drug resistance. This work provides new insight into how the physical properties of biofilms affect dispersal and drug resistance and suggests new potential antifungal strategies that could be effective against biofilms.
authors.affiliation: cnobile@ucmerced.edu.
authors.forename: Clarissa J
authors.initials: CJ
authors.lastname: Nobile
authors.forename: Emily P
authors.initials: EP
authors.lastname: Fox
authors.affiliation: Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Nairi
authors.initials: N
authors.lastname: Hartooni
authors.affiliation: Department of Medicine, University of Wisconsin, Madison, Wisconsin, USA.
authors.forename: Kaitlin F
authors.initials: KF
authors.lastname: Mitchell
authors.affiliation: Medical University Vienna, Max F. Perutz Laboratories, Vienna, Austria.
authors.forename: Denes
authors.initials: D
authors.lastname: Hnisz
authors.affiliation: Department of Medicine, University of Wisconsin, Madison, Wisconsin, USA.
authors.forename: David R
authors.initials: DR
authors.lastname: Andes
authors.affiliation: Medical University Vienna, Max F. Perutz Laboratories, Vienna, Austria.
authors.forename: Karl
authors.initials: K
authors.lastname: Kuchler
authors.affiliation: Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Alexander D
authors.initials: AD
authors.lastname: Johnson
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology*; D018441:Biofilms; D002176:Candida albicans / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics / Q000502:physiology*; D002177:Candidiasis / Q000382:microbiology*; D025141:Drug Resistance, Fungal; D015725:Fluconazole / Q000494:pharmacology; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008826:Microbial Sensitivity Tests
chemical_list: D000935:Antifungal Agents; D005656:Fungal Proteins; D015725:Fluconazole; D006655:Histone Deacetylases