Aspartyl proteinases of Candida albicans and their role in pathogenicity

2001 ◽  
Vol 39 (4) ◽  
pp. 303-313 ◽  
Author(s):  
F. de Bernardis ◽  
P. A. Sullivan ◽  
A. Cassone
Keyword(s):  
Candida Albicans ◽  
Aspartyl Proteinases

scholarly journals Secreted Aspartyl Proteinases and Interactions of Candida albicans with Human Endothelial Cells

1998 ◽  
Vol 66 (6) ◽  
pp. 3003-3005 ◽  
Author(s):  
Ashraf S. Ibrahim ◽  
Scott G. Filler ◽  
Dominique Sanglard ◽  
John E. Edwards ◽  
Bernhard Hube
Keyword(s):  
Endothelial Cells ◽  
Candida Albicans ◽  
Endothelial Cell ◽  
Cell Interactions ◽  
Human Endothelial Cells ◽  
Secreted Aspartyl Proteinase ◽  
Null Mutants ◽  
Aspartyl Proteinases

ABSTRACT The endothelial cell interactions of homozygous null mutants ofCandida albicans that were deficient in secreted aspartyl proteinase 1 (Sap1), Sap2, or Sap3 were investigated. Only Sap2 was found to contribute to the ability of C. albicans to damage endothelial cells and stimulate them to express E-selectin. None of the Saps studied appears to play a role in C. albicansadherence to endothelial cells.

scholarly journals Limited Role of Secreted Aspartyl Proteinases Sap1 to Sap6 in Candida albicans Virulence and Host Immune Response in Murine Hematogenously Disseminated Candidiasis

2010 ◽  
Vol 78 (11) ◽  
pp. 4839-4849 ◽  
Author(s):  
Alexandra Correia ◽  
Ulrich Lermann ◽  
Luzia Teixeira ◽  
Filipe Cerca ◽  
Sofia Botelho ◽  
...  
Keyword(s):  
Immune Response ◽  
Candida Albicans ◽  
Significant Role ◽  
Murine Model ◽  
Null Mutant ◽  
Wild Type ◽  
Survival Times ◽  
Disseminated Candidiasis ◽  
Mutant Strains ◽  
Aspartyl Proteinases

ABSTRACTCandida albicanssecreted 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 ofsap-null mutant strains. However, the exclusive contribution ofSAPgenes 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 ofSAP1toSAP6in a murine model of hematogenously disseminated candidiasis usingsap-null mutant strains not affected in theirURA3gene expression and compared their virulence phenotypes with those of Ura-blastersapmutants. The median survival time of BALB/c mice intravenously infected with a mutant strain lackingSAP1toSAP3was equivalent to that of mice infected with wild-type strain SC5314, while those infected with mutant strains lackingSAP5showed slightly extended survival times. Nevertheless, no differences could be observed between the wild type and a Δsap456mutant in their abilities to invade mouse kidneys. Likewise, a deficiency inSAP4toSAP6had no noticeable impact on the immune response elicited in the spleens and kidneys ofC. 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 inC. albicansvirulence in a murine model of hematogenously disseminated candidiasis and that, in this model, Sap1 to Sap3 are not necessary for successfulC. albicansinfection.

scholarly journals Candida albicans Secreted Aspartyl Proteinases in Virulence and Pathogenesis

2003 ◽  
Vol 67 (3) ◽  
pp. 400-428 ◽  
Author(s):  
Julian R. Naglik ◽  
Stephen J. Challacombe ◽  
Bernhard Hube
Keyword(s):  
Candida Albicans ◽  
Proteinase Inhibitors ◽  
Host Immune System ◽  
Human Proteins ◽  
Candida Infections ◽  
Human Infections ◽  
Host Cell Membranes ◽  
Aspartyl Proteinases

SUMMARY Candida albicans is the most common fungal pathogen of humans and has developed an extensive repertoire of putative virulence mechanisms that allows successful colonization and infection of the host under suitable predisposing conditions. Extracellular proteolytic activity plays a central role in Candida pathogenicity and is produced by a family of 10 secreted aspartyl proteinases (Sap proteins). Although the consequences of proteinase secretion during human infections is not precisely known, in vitro, animal, and human studies have implicated the proteinases in C. albicans virulence in one of the following seven ways: (i) correlation between Sap production in vitro and Candida virulence, (ii) degradation of human proteins and structural analysis in determining Sap substrate specificity, (iii) association of Sap production with other virulence processes of C. albicans, (iv) Sap protein production and Sap immune responses in animal and human infections, (v) SAP gene expression during Candida infections, (vi) modulation of C. albicans virulence by aspartyl proteinase inhibitors, and (vii) the use of SAP-disrupted mutants to analyze C. albicans virulence. Sap proteins fulfill a number of specialized functions during the infective process, which include the simple role of digesting molecules for nutrient acquisition, digesting or distorting host cell membranes to facilitate adhesion and tissue invasion, and digesting cells and molecules of the host immune system to avoid or resist antimicrobial attack by the host. We have critically discussed the data relevant to each of these seven criteria, with specific emphasis on how this proteinase family could contribute to Candida virulence and pathogenesis.

Expression of Secreted Aspartyl Proteinases in an Experimental Model of Candida albicans -Associated Denture Stomatitis

2015 ◽  
Vol 25 (2) ◽  
pp. 127-134 ◽  
Author(s):  
Priscila Lie Tobouti ◽  
Ana Regina Casaroto ◽  
Ricardo Sérgio Couto de Almeida ◽  
Solange de Paula Ramos ◽  
Thiago José Dionísio ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Experimental Model ◽  
Denture Stomatitis ◽  
Aspartyl Proteinases

scholarly journals Effect of antimycotic agents on the activity of aspartyl proteinases secreted by Candida albicans

2003 ◽  
Vol 52 (3) ◽  
pp. 247-249 ◽  
Author(s):  
Martin Schaller ◽  
Nikola Krnjaic ◽  
Markus Niewerth ◽  
Gerald Hamm ◽  
Bernhard Hube ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Amphotericin B ◽  
Proteinase Inhibitors ◽  
Inhibitory Effect ◽  
Antifungal Drugs ◽  
Immunodeficiency Virus ◽  
Antimycotic Agent ◽  
Pepstatin A ◽  
Aspartyl Proteinases

The inhibitory effect of human immunodeficiency virus (HIV) proteinase inhibitors amprenavir and saquinavir and antifungal agents terbinafine, ketoconazole, amphotericin B and ciclopiroxolamine on aspartyl proteinases (Saps) secreted by Candida albicans was tested in an in vitro spectophotometric assay. As expected, both HIV proteinase inhibitors showed a significant inhibitory effect on Sap activity, which was comparable to that of the classical aspartyl proteinase inhibitor pepstatin A (P < 0.001). Antifungal drugs such as ketoconazole, terbinafine and amphotericin B had no, or only minor, inhibitory effects on proteolytic activity. In contrast, a significant reduction in Sap activity could be demonstrated during treatment with the antifungal agent ciclopiroxolamine (P < 0.001). These results point to a multiple effect of this antimycotic agent and might explain the reduced adherence of C. albicans to human epithelial cells at subinhibitory doses.

scholarly journals Intravaginal and Intranasal Immunizations Are Equally Effective in Inducing Vaginal Antibodies and Conferring Protection against Vaginal Candidiasis

2002 ◽  
Vol 70 (5) ◽  
pp. 2725-2729 ◽  
Author(s):  
Flavia De Bernardis ◽  
Maria Boccanera ◽  
Daniela Adriani ◽  
Antonietta Girolamo ◽  
Antonio Cassone
Keyword(s):  
Candida Albicans ◽  
Cholera Toxin ◽  
Vaginal Candidiasis ◽  
Vaginal Infection ◽  
Intranasal Route ◽  
Mucosal Adjuvant ◽  
Degree Of Protection ◽  
Fungal Antigens ◽  
High Degree ◽  
Aspartyl Proteinases

ABSTRACT Oophorectomized, estrogen-treated rats were immunized by the intravaginal or intranasal route with a mannoprotein extract (MP) or secreted aspartyl proteinases (Sap) of Candida albicans, with or without cholera toxin as a mucosal adjuvant. Both routes of immunization were equally effective in (i) inducing anti-MP and anti-Sap vaginal antibodies and (ii) conferring a high degree of protection against the vaginal infection by the fungus. These data suggest that appropriate fungal antigens and adjuvant can be used to protect against candidal vaginitis, by either route.

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

2001 ◽  
Vol 50 (8) ◽  
pp. 743-747 ◽  
Author(s):  
MARTIN SCHALLER ◽  
ELFRIEDE JANUSCHKE ◽  
CAROLIN SCHACKERT ◽  
BIRGIT WOERLE ◽  
HANS C. KORTING
Keyword(s):  
Candida Albicans ◽  
Aspartyl Proteinases
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