Differential Expression of Secretory Aspartyl Proteinase Genes (
 SAP1
 -
 10
 ) in Oral
 Candida albicans
 Isolates with Distinct Karyotypes

Tavanti, Arianna; Pardini, Giacomo; Campa, Daniele; Davini, Paola; Lupetti, Antonella; Senesi, Sonia

doi:10.1128/jcm.42.10.4726-4734.2004

Cited by 30 publications

(21 citation statements)

References 40 publications

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“…However, cross-sectional studies of C. albicans SAP gene expression in human OPC showed that SAP2, as well as SAP4 to SAP6, were predominantly expressed in OPC patients, as well as Candida carriers (5,(13)(14)(15)(16). C. albicans recovered from murine OPC showed that Sap4 to -6 were highly expressed during infection; however, other studies found a role for Sap1 to -6 in fungal invasion and damage to oral and vaginal epithelial mucosal surfaces (5,14,(16)(17)(18)(19)(20)(21). Thus, functional analyses of the abilities of individual Saps to promote virulence in mucosal infection has been inconclusive, due to different expression levels during the course of infection.…”

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confidence: 99%

Novel Aggregation Properties of Candida albicans Secreted Aspartyl Proteinase Sap6 Mediate Virulence in Oral Candidiasis

et al. 2015

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Candida albicans, a commensal fungus of the oral microbiome, causes oral candidiasis in humans with localized or systemic immune deficiencies. Secreted aspartic proteinases (Saps) are a family of 10 related proteases and are virulence factors due to their proteolytic activity, as well as their roles in adherence and colonization of host tissues. We found that mice infected sublingually with C. albicans cells overexpressing Sap6 (SAP6 OE and a ⌬sap8 strain) had thicker fungal plaques and more severe oral infection, while infection with the ⌬sap6 strain was attenuated. These hypervirulent strains had highly aggregative colony structure in vitro and higher secreted proteinase activity; however, the levels of proteinase activity of C. albicans Saps did not uniformly match their abilities to damage cultured oral epithelial cells (SCC-15 cells). Hyphal induction in cells overexpressing Sap6 (SAP6 OE and ⌬sap8 cells) resulted in formation of large cell-cell aggregates. These aggregates could be produced in germinated wild-type cells by addition of native or heat-inactivated Sap6. Sap6 bound only to germinated cells and increased C. albicans adhesion to oral epithelial cells. The adhesion properties of Sap6 were lost upon deletion of its integrin-binding motif (RGD) and could be inhibited by addition of RGD peptide or anti-integrin antibodies. Thus, Sap6 (but not Sap5) has an alternative novel function in cell-cell aggregation, independent of its proteinase activity, to promote infection and virulence in oral candidiasis. Candida albicans is a commensal fungus that is often part of the oral microflora of healthy people. Loss of host immunity, HIV infection, corticosteroid use, or alteration of the oral microflora following antibiotic therapies permits a pathogenic transition of C. albicans to cause oropharyngeal candidiasis (OPC) (1, 2). Acute pseudomembranous candidiasis is one of the most common forms of OPC, in which C. albicans forms white patches on the surface of the buccal mucosa, tongue, or soft palate. These superficial fungal plaques can be lifted from underlying tissues for purposes of clinical diagnosis and analysis (3).C. albicans expresses specific sets of virulence factors that promote hypha formation and adhesion and invasion of host tissues (4). Secreted aspartyl proteinases (Saps) are recognized virulence factors because they degrade host proteins to provide nitrogen for fungal cell metabolism, contribute to adherence, facilitate fungal epithelial and endothelial penetration, and are immunogenic during infection (5-7). Microbial proteinases are classified as serine, cysteine, metallo-, or aspartyl proteinases according to the site of catalytic hydrolysis of substrate peptide bonds; however, C. albicans produces only aspartyl proteinases (5, 6).C. albicans expresses a family of 10 SAP genes that are clustered into groups SAP1 to SAP3, SAP4 to SAP6, SAP7, SAP8, and SAP9 and SAP10 based upon their sequence homologies and pH activities (8, 9). Sap1 through Sap8 are processed and transported via the secreto...

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Novel Aggregation Properties of Candida albicans Secreted Aspartyl Proteinase Sap6 Mediate Virulence in Oral Candidiasis

et al. 2015

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“…Regardless of the site of isolation, Sap 2 has been shown to be preferentially expressed by yeast-forming fungi in media containing bovine serum albumin as the protein substrate (14). Among the enzymatic properties of Sap 2 described in the literature, the proteolysis of collagen (30), the decreased efficiency of phagocytosis by polymorphonuclear neutrophils (3), and the activation of the proinflammatory cytokine interleukin-1 beta (31, 32) may contribute to bone resorption in the periapex, thus playing an important role in the onset and progression of apical periodontitis.…”

Section: Discussionmentioning

confidence: 99%

“…Various studies (2,6,14,16) have emphasized that the ability to degrade protein substrates is an important contribution to the establishment of C. albicans infections in various organic environments. Specifically, the increased proteolytic activity among strains isolated from necrotic root canals suggests that these microorganisms can participate in establishing and maintaining endodontic infections although this remains to be shown experimentally.…”

Section: Discussionmentioning

confidence: 99%

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Differential Proteinase Patterns among Candida albicans Strains Isolated from Root Canal and Lingual Dorsum: Possible Roles in Periapical Disease

Miranda

Vianna

Rodrigues

et al. 2015

Journal of Endodontics

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“…Mendes et al (2007) showed that biofilms of C. albicans consistently secrete more Saps than their planktonic counterparts, suggesting that increased Sap production is yet another mechanism by which yeasts persist on host surfaces, in addition to the expression of the foregoing virulence attributes. Another intriguing observation is that the Sap-encoding genes SAP1-10 were differentially expressed in C. albicans oral isolates that possess distinct genome backgrounds, referred to as b and c karyotype profiles, in which the c karyotype express a higher number of SAP1-10 genes than b-type strains during their in vitro propagation (Tavanti et al 2004). The host immune system is the major factor determining whether this opportunistic yeast behaves as a commensal or as a pathogen.…”

Section: Candida Sppmentioning

confidence: 98%

Aspartic Peptidase Inhibitors as Potential Bioactive Pharmacological Compounds Against Human Fungal Pathogens

Santos

2010

Combating Fungal Infections

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The development of novel antifungal drugs is becoming more demanding every day since existing drugs either have too many side-effects or they tend to lose effectiveness due to resistant fungal strains. In view of this, a number of new strategies to obstruct fungal biological processes have emerged; one of them is focused on peptidase inhibition. This particular class of hydrolytic enzymes cleaves peptide bond in proteinaceous substrates, a reaction extremely important in maintaining the physiology of all living cells. Interestingly, peptidases are also essential virulence factors for prokaryotic and eukaryote micro-organisms, including fungi, during all stages of the infection process. Consequently, peptidases are potential targets for the development of future antifungal drugs. This chapter will focus on the potential use of aspartic peptidase inhibitors against human fungal pathogens, showing the capability of these bioactive pharmacological compounds to arrest vital fungal processes such as growth, differentiation, nutrition, and interaction with host components.

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Differential Expression of Secretory Aspartyl Proteinase Genes ( SAP1 - 10 ) in Oral Candida albicans Isolates with Distinct Karyotypes

Abstract: Two karyotypes of oral

Cited by 30 publications

References 40 publications

Novel Aggregation Properties of Candida albicans Secreted Aspartyl Proteinase Sap6 Mediate Virulence in Oral Candidiasis

Novel Aggregation Properties of Candida albicans Secreted Aspartyl Proteinase Sap6 Mediate Virulence in Oral Candidiasis

Differential Proteinase Patterns among Candida albicans Strains Isolated from Root Canal and Lingual Dorsum: Possible Roles in Periapical Disease

Aspartic Peptidase Inhibitors as Potential Bioactive Pharmacological Compounds Against Human Fungal Pathogens

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