Author:

Keywords:

Science & Technology, Life Sciences & Biomedicine, Microbiology, Mycology, GENE-EXPRESSION, PSI+ PRION, IN-VIVO, SACCHAROMYCES-CEREVISIAE, FUNGAL PATHOGEN, YEAST, THERMOTOLERANCE, STRESS, Animals, Biofilms, Caenorhabditis elegans, Candida albicans, Candidiasis, Disease Models, Animal, Fungal Proteins, Gene Deletion, Heat-Shock Proteins, 06 Biological Sciences, 11 Medical and Health Sciences

Abstract:

The consequences of deprivation of the molecular chaperone Hsp104 in the fungal pathogen Candida albicans were investigated. Mutants lacking HSP104 became hypersusceptible to lethally-high temperatures, similarly to the corresponding mutants of Saccharomyces cerevisiae, whereas normal susceptibility was restored upon reintroduction of the gene. By use of a strain whose only copy of HSP104 is an ectopic gene under the control of a tetracycline-regulated promoter, expression of Hsp104 prior to the administration of heat shock could be demonstrated to be sufficient to confer protection from the subsequent temperature increase. This result points to a key role for Hsp104 in orchestrating the cell response to elevated temperatures. Despite not showing evident growth or morphological defects, biofilm formation by cells lacking Hsp104 proved defective in two established in vitro models that use polystyrene and polyurethane as the substrate, respectively. Biofilms formed by the wild type and HSP104 reconstituted strain showed patterns of intertwined hyphae in extracellular matrix. By contrast, biofilm formed by the hsp104/hsp104mutant showed structural defects and appeared patchy and loose. Decreased virulence of the hsp104/hsp104mutant was observed in the Caenorhabditis elegans infection model, in which high in vivo temperature does not play a role. In agreement with the view that stress responses in fungal pathogens may have evolved to provide niche-specific adaptation to environmental conditions, these results provide an indication toward a temperature-independent role for Hsp104 in support of Candida albicans virulence, in addition to its key role in governing thermotolerance.