Hsp90 Governs Dispersion and Drug Resistance of Fungal Biofilms

• DOI: 10.1371/journal.ppat.1002257
• Publication Date: 2011-09-09T04:40:12Z
• Authors: Nicole Robbins; Priya Uppuluri; Jeniel Nett; Ranjith Rajendran; Gordon Ramage; Jose L. Lopez-Ribot; David Andes; Leah E. Cowen
• Keywords: Antifungal drugs

Fungal biofilms are a major cause of human mortality and recalcitrant to most treatments due intrinsic drug resistance. These complex communities multiple cell types form on indwelling medical devices their eradication often requires surgical removal infected devices. Here we implicate the molecular chaperone Hsp90 as key regulator biofilm dispersion We previously established that in leading fungal pathogen, Candida albicans, enables emergence maintenance resistance planktonic conditions by stabilizing protein phosphatase calcineurin MAPK Mkc1. also regulates temperature-dependent C. albicans morphogenesis through repression cAMP-PKA signalling. demonstrate genetic depletion reduced growth maturation vitro impaired dispersal cells. Further, compromising function abrogated widely deployed class antifungal drugs, azoles. Depletion led reduction Mkc1 but not conditions, suggesting different mechanisms these distinct cellular states. Reduction levels marked decrease matrix glucan levels, providing compelling mechanism which might regulate azole Impairment genetically or pharmacologically transformed fluconazole from ineffectual highly effective eradicating rat venous catheter infection model. Finally, inhibition lethal mould, Aspergillus fumigatus, newest antifungals reach clinic, echinocandins. Thus, establish novel regulating targeting provides much-needed strategy for improving clinical outcome treatment infections.