Genetic basis of Candida biofilm resistance due to drug-sequestering matrix glucan.
Medical devices provide an ecological niche for microbes to flourish as a biofilm community, protected from antimicrobials and host defenses. Biofilms formed by Candida albicans, the most common fungal pathogen, survive exposure to extraordinarily high drug concentrations. Here, we show that beta-glucan synthase Fks1p produces glucan, which is deposited in the biofilm matrix. The extracellular glucan is required for biofilm resistance and acts by sequestering antifungals, rendering cells resistant to their action. These findings provide the genetic basis for how biofilm matrix production governs drug resistance by impeding drug diffusion and also identify a useful biofilm drug target.
Nett
Jeniel E
JE
Department of Medicine, University of Wisconsin, Madison, WI 53792, USA.
Sanchez
Hiram
H
Cain
Michael T
MT
Andes
David R
DR
D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology* / Q000627:therapeutic use; D018441:Biofilms / Q000254:growth & development*; D002175:Candida / Q000235:genetics* / Q000502:physiology* / Q000648:ultrastructure; D002177:Candidiasis / Q000188:drug therapy / Q000382:microbiology; D004305:Dose-Response Relationship, Drug; D025141:Drug Resistance, Fungal / Q000235:genetics*; D015725:Fluconazole / Q000494:pharmacology; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D005936:Glucans / Q000378:metabolism*; D051379:Mice; D051381:Rats
D000935:Antifungal Agents; D005656:Fungal Proteins; D005936:Glucans; D015725:Fluconazole