Evidence that Members of the Secretory Aspartyl Proteinase Gene Family, in Particular<i>SAP2,</i>Are Virulence Factors for<i>Candida</i>Vaginitis

Bernardis, Flavia De; Arancia, Silvia; Morelli, L; Hube, Bernhard; Sanglard, Dominique; Schäfer, Wilhelm; Cassone, Antonio

doi:10.1086/314546

Cited by 160 publications

(158 citation statements)

References 40 publications

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“…albicans colonizes and infects more host niches in addition to those analyzed in our present study, for example the oral cavity or the vagina. Because the environmental conditions at these sites differ from other locations, C. albicans probably adapts to these niches by the expression of different sets of SAP and other virulence genes (16,30,31), which is supported by the results obtained with specific mutants (32). As a consequence of the differential expression of individual SAP genes at various stages of the infection, one would expect that the individual SAP isoenzymes differ with respect to their biochemical properties, allowing the fungus to use the proteinase that is best adapted to a certain environment and for a specific function.…”

Section: Discussionmentioning

confidence: 69%

Differential activation of a Candida albicans virulence gene family during infection

Staib¹,

Kretschmar²,

Nichterlein³

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

147

138

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The yeast Candida albicans is a harmless commensal in most healthy people, but it causes superficial as well as life-threatening systemic infections in immunocompromised patients. C. albicans can colonize or infect virtually all body sites because of its high adaptability to different host niches, which involves the activation of appropriate sets of genes in response to complex environmental signals. We have used an in vivo expression technology that is based on genetic recombination as a reporter of gene expression to monitor the differential activation of individual members of a gene family encoding secreted aspartic proteinases (Saps), which have been implicated in C. albicans virulence, at various stages of the infection process. Our results demonstrate that SAP expression depends on the type of infection, with different SAP isogenes being activated during systemic disease as compared with mucosal infection. In addition, the activation of individual SAP genes depends on the progress of the infection, some members of the gene family being induced immediately after contact with the host, whereas others are expressed only after dissemination into deep organs. In the latter case, the number of invading organisms determines whether induction of a virulence gene is necessary for successful infection. The in vivo expression technology allows the elucidation of gene expression patterns at different stages of the fungus-host interaction, thereby revealing regulatory adaptation mechanisms that make C. albicans the most successful fungal pathogen of humans and, at the same time, identifying the stage of an infection at which certain virulence genes may play a role.

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Section: Discussionmentioning

confidence: 69%

Differential activation of a Candida albicans virulence gene family during infection

Staib¹,

Kretschmar²,

Nichterlein³

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

147

138

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“…The relevance of SAP1±3 for mucosal and cutaneous candidosis has also been illustrated by gene expression studies [6, 9±11] and infection experiments with SAP null mutants [10,11,14,15,21]. The importance of SAP1-3 for infection in vivo is supported by analysis of …”

Section: Discussionmentioning

confidence: 98%

Different isoforms of secreted aspartyl proteinases (Sap) are expressed by Candida albicans during oral and cutaneous candidosis in vivo

Schaller

Januschke

Schackert

et al. 2001

Journal of Medical Microbiology

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“…Initially it was demonstrated that sap1D, sap2D and sap3D single mutants as well as triple mutants lacking the highly homologous SAP4-SAP6 genes exhibited attenuated virulence after intravenous infection of mice, indicating that all these genes have important roles for the normal progression of a systemic infection Sanglard et al, 1997). Mutants deleted for either SAP1, SAP2 or SAP3 were also found to be less virulent in a rat model of Candida vaginitis, whereas mutants lacking SAP4-SAP6 did not exhibit a detectable virulence defect under these conditions (De Bernardis et al, 1999). Conversely, only the latter mutants showed reduced virulence in a murine model of Candida peritonitis, while deletion of SAP1, SAP2 or SAP3 had no significant effect in this infection model .…”

Section: Introductionmentioning

confidence: 88%

Secreted aspartic proteases are not required for invasion of reconstituted human epithelia by Candida albicans

2008

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A well-known virulence attribute of the human-pathogenic yeast Candida albicans is the secretion of aspartic proteases (Saps), which may contribute to colonization and infection of different host niches by degrading tissue barriers, destroying host defence molecules, or digesting proteins for nutrient supply. The role of individual Sap isoenzymes, which are encoded by a large gene family, for the pathogenicity of C. albicans has been investigated by assessing the virulence of mutants lacking specific SAP genes and by studying the expression pattern of the SAP genes in various models of superficial and systemic infections. We used a recombination-based genetic reporter system to detect the induction of the SAP1-SAP6 genes during infection of reconstituted human vaginal epithelium. Only SAP5, but none of the other tested SAP genes, was detectably activated in this in vitro infection model. To directly address the importance of the SAP1-SAP6 genes for invasion of reconstituted human epithelia (RHE), we constructed a set of mutants of the wild-type C. albicans model strain SC5314 in which either single or multiple SAP genes were specifically deleted. Even mutants lacking all of the SAP1-SAP3 or the SAP4-SAP6 genes displayed the same capacity to invade and damage both oral and vaginal RHE as their wild-type parental strain, in contrast to a nonfilamentous efg1D mutant that was avirulent under these conditions. We therefore conclude from these results that the secreted aspartic proteases Sap1p-Sap6p are not required for invasion of RHE by C. albicans.

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Evidence that Members of the Secretory Aspartyl Proteinase Gene Family, in ParticularSAP2,Are Virulence Factors forCandidaVaginitis

Cited by 160 publications

References 40 publications

Differential activation of a Candida albicans virulence gene family during infection

Differential activation of a Candida albicans virulence gene family during infection

Different isoforms of secreted aspartyl proteinases (Sap) are expressed by Candida albicans during oral and cutaneous candidosis in vivo

Secreted aspartic proteases are not required for invasion of reconstituted human epithelia by Candida albicans

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