Disruption of the Candida albicans ATC1 gene encoding a cell-linked acid trehalase decreases hypha formation and infectivity without affecting resistance to oxidative stress.
In Candida albicans, the ATC1 gene, encoding a cell wall-associated acid trehalase, has been considered as a potentially interesting target in the search for new antifungal compounds. A phenotypic characterization of the double disruptant atc1Delta/atc1Delta mutant showed that it was unable to grow on exogenous trehalose as sole carbon source. Unlike actively growing cells from the parental strain (CAI4), the atc1Delta null mutant displayed higher resistance to environmental insults, such as heat shock (42 degrees C) or saline exposure (0.5 M NaCl), and to both mild and severe oxidative stress (5 and 50 mM H(2)O(2)), which are relevant during in vivo infections. Parallel measurements of intracellular trehalose and trehalose-metabolizing enzymes revealed that significant amounts of the disaccharide were stored in response to thermal and oxidative challenge in the two cell types. The antioxidant activities of catalase and glutathione reductase were triggered by moderate oxidative exposure (5 mM H(2)O(2)), whereas superoxide dismutase was inhibited dramatically by H(2)O(2), where a more marked decrease was observed in atc1Delta cells. In turn, the atc1Delta mutant exhibited a decreased capacity of hypha and pseudohypha formation tested in different media. Finally, the homozygous null mutant in a mouse model of systemic candidiasis displayed strongly reduced pathogenicity compared with parental or heterozygous strains. These results suggest not only a novel role for the ATC1 gene in dimorphism and infectivity, but also that an interconnection between stress resistance, dimorphic conversion and virulence in C. albicans may be reconsidered. They also support the hypothesis that Atc1p is not involved in the physiological hydrolysis of endogenous trehalose.
Pedreño
Yolanda
Y
Departamento de Microbiología y Ecología, Universidad de Valencia, E-46100 Burjassot, Valencia, Spain.|Área de Microbiología, Facultad de Biología, Universidad de Murcia, E-30071 Murcia, Spain.
González-Párraga
Pilar
P
Área de Microbiología, Facultad de Biología, Universidad de Murcia, E-30071 Murcia, Spain.
Martínez-Esparza
María
M
Departamento de Bioquímica y Biología Molecular B e Inmunología, Universidad de Murcia, E-30071 Murcia, Spain.
Sentandreu
Rafael
R
Departamento de Microbiología y Ecología, Universidad de Valencia, E-46100 Burjassot, Valencia, Spain.
Valentín
Eulogio
E
Departamento de Microbiología y Ecología, Universidad de Valencia, E-46100 Burjassot, Valencia, Spain.
Argüelles
Juan-Carlos
JC
Área de Microbiología, Facultad de Biología, Universidad de Murcia, E-30071 Murcia, Spain.
D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology; D002176:Candida albicans / Q000166:cytology / Q000201:enzymology* / Q000235:genetics / Q000254:growth & development / Q000472:pathogenicity*; D002177:Candidiasis; D002374:Catalase / Q000032:analysis; D004195:Disease Models, Animal; D005260:Female; D017353:Gene Deletion; D005980:Glutathione Reductase / Q000032:analysis; D006358:Hot Temperature; D006861:Hydrogen Peroxide / Q000494:pharmacology; D025301:Hyphae / Q000235:genetics / Q000254:growth & development*; D051379:Mice; D050296:Microbial Viability; D009024:Morphogenesis / Q000235:genetics*; D009997:Osmotic Pressure; D018384:Oxidative Stress / Q000502:physiology*; D013482:Superoxide Dismutase / Q000032:analysis; D016019:Survival Analysis; D014198:Trehalase / Q000235:genetics / Q000502:physiology*; D014199:Trehalose / Q000032:analysis; D014774:Virulence / Q000235:genetics*
D000935:Antifungal Agents; D014199:Trehalose; D006861:Hydrogen Peroxide; D002374:Catalase; D013482:Superoxide Dismutase; D005980:Glutathione Reductase; D014198:Trehalase