Evidence that members of the secretory aspartyl proteinase gene family, in particular SAP2, are virulence factors for Candida vaginitis.
Virulence of Candida albicans strains with targeted disruption of secretory aspartyl proteinase genes (SAP1 to SAP6) was assessed in an estrogen-dependent rat vaginitis model. Null sap1 to sap3 but not sap4 to sap6 mutants lost most of the virulence of their parental strain SC5314. In particular, the sap2 mutant was almost avirulent in this model. Reinsertion of the SAP2 gene into this latter mutant led to the to recovery of the vaginopathic potential. The vaginal fluids of the animals infected by the wild type strain or by the sap1 or sap3 mutants expressed a pepstatin-sensitive proteinase activity in vitro. No traces of this activity were found in the vaginal fluid of rats challenged by the sap2 mutant. All strains were capable of developing true hyphae during infection. Thus, members of SAP family, in particular SAP2, play a clear pathogenic role in vaginitis and may constitute a novel target for chemoimmunotherapy of this infection.
De Bernardis
F
F
Laboratory of Bacteriology, Department of Veterinary Medicine, Istituto Superiore di Sanitá, Rome, Italy.
Arancia
S
S
Morelli
L
L
Hube
B
B
Sanglard
D
D
Schäfer
W
W
Cassone
A
A
D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000235:genetics*; D001483:Base Sequence; D002176:Candida albicans / Q000201:enzymology / Q000235:genetics* / Q000472:pathogenicity*; D002177:Candidiasis / Q000382:microbiology*; D017931:DNA Primers / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D005656:Fungal Proteins; D017353:Gene Deletion; D005800:Genes, Fungal; D005810:Multigene Family; D016133:Polymerase Chain Reaction; D051381:Rats; D017208:Rats, Wistar; D014627:Vaginitis / Q000382:microbiology*; D014774:Virulence / Q000235:genetics
D017931:DNA Primers; D005656:Fungal Proteins; D016282:Aspartic Acid Endopeptidases; C086390:SAP1 protein, Candida albicans; C090753:SAP2 protein, Candida; C090754:SAP3 protein, Candida albicans; C086392:SAP4 protein, Candida albicans; C090755:SAP5 protein, Candida albicans