The heat-induced molecular disaggregase Hsp104 of Candida albicans plays a role in biofilm formation and pathogenicity in a worm infection model.
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 their not showing evident growth or morphological defects, biofilm formation by cells lacking HSP104 proved to be defective in two established in vitro models that use polystyrene and polyurethane as the substrates. Biofilms formed by the wild-type and HSP104-reconstituted strains showed patterns of intertwined hyphae in the extracellular matrix. In contrast, biofilm formed by the hsp104Δ/hsp104Δ mutant showed structural defects and appeared patchy and loose. Decreased virulence of the hsp104Δ/hsp104Δ 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 of a temperature-independent role for Hsp104 in support of Candida albicans virulence, in addition to its key role in governing thermotolerance.
Department of Molecular Microbiology, VIB, Katholieke Universiteit Leuven, Leuven, Belgium. Alessandro.Fiori@mmbio.vib-kuleuven.be
Alessandro
A
Fiori
Sona
S
Kucharíková
Gilmer
G
Govaert
Bruno P A
BP
Cammue
Karin
K
Thevissen
Patrick
P
Van Dijck
D000818:Animals; D018441:Biofilms / Q000254:growth & development*; D017173:Caenorhabditis elegans / Q000382:microbiology; D002176:Candida albicans / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology; D002177:Candidiasis / Q000382:microbiology; D004195:Disease Models, Animal; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*
D005656:Fungal Proteins; D006360:Heat-Shock Proteins