title: Limited role of secreted aspartyl proteinases Sap1 to Sap6 in Candida albicans virulence and host immune response in murine hematogenously disseminated candidiasis.
abstract: Candida albicans secreted aspartyl proteinases (Saps) are considered virulence-associated factors. Several members of the Sap family were claimed to play a significant role in the progression of candidiasis established by the hematogenous route. This assumption was based on the observed attenuated virulence of sap-null mutant strains. However, the exclusive contribution of SAP genes to their attenuated phenotype was not unequivocally confirmed, as the Ura status of these mutant strains could also have contributed to the attenuation. In this study, we have reassessed the importance of SAP1 to SAP6 in a murine model of hematogenously disseminated candidiasis using sap-null mutant strains not affected in their URA3 gene expression and compared their virulence phenotypes with those of Ura-blaster sap mutants. The median survival time of BALB/c mice intravenously infected with a mutant strain lacking SAP1 to SAP3 was equivalent to that of mice infected with wild-type strain SC5314, while those infected with mutant strains lacking SAP5 showed slightly extended survival times. Nevertheless, no differences could be observed between the wild type and a Δsap456 mutant in their abilities to invade mouse kidneys. Likewise, a deficiency in SAP4 to SAP6 had no noticeable impact on the immune response elicited in the spleens and kidneys of C. albicans-infected mice. These results contrast with the behavior of equivalent Ura-blaster mutants, which presented a significant reduction in virulence. Our results suggest that Sap1 to Sap6 do not play a significant role in C. albicans virulence in a murine model of hematogenously disseminated candidiasis and that, in this model, Sap1 to Sap3 are not necessary for successful C. albicans infection.
authors.affiliation: Centre of Molecular and Environmental Biology (CBMA), Department of Biology, University of Minho, Braga, Portugal.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Correia
authors.forename: Ulrich
authors.initials: U
authors.lastname: Lermann
authors.forename: Luzia
authors.initials: L
authors.lastname: Teixeira
authors.forename: Filipe
authors.initials: F
authors.lastname: Cerca
authors.forename: Sofia
authors.initials: S
authors.lastname: Botelho
authors.forename: Rui M Gil
authors.initials: RM
authors.lastname: da Costa
authors.forename: Paula
authors.initials: P
authors.lastname: Sampaio
authors.forename: Fátima
authors.initials: F
authors.lastname: Gärtner
authors.forename: Joachim
authors.initials: J
authors.lastname: Morschhäuser
authors.forename: Manuel
authors.initials: M
authors.lastname: Vilanova
authors.forename: Célia
authors.initials: C
authors.lastname: Pais
mesh_terms: D000818:Animals; D057055:Aspartic Acid Proteases / Q000235:genetics / Q000378:metabolism*; D002176:Candida albicans / Q000201:enzymology / Q000472:pathogenicity*; D002177:Candidiasis / Q000276:immunology* / Q000382:microbiology / Q000401:mortality; D004195:Disease Models, Animal; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D007668:Kidney / Q000276:immunology / Q000382:microbiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D013154:Spleen / Q000276:immunology / Q000382:microbiology; D014774:Virulence
chemical_list: D005656:Fungal Proteins; D057055:Aspartic Acid Proteases