Cited by 1,179Antifungal resistance and susceptibilityFungal and yeast genetics researchFungal Infections and Studies

Candida albicans Secreted Aspartyl Proteinases in Virulence and Pathogenesis

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Naglik, Julian R., Challacombe, Stephen J., Hube, Bernhard·2003·Microbiology and Molecular Biology Reviews

Abstract

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.

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Authors
Naglik, J. R., Challacombe, S. J., & Hube, B.
Affiliations
  • King's College London (GB)
  • Robert Koch Institute (DE)
Corresponding author
Naglik, Julian R.
Venue
Microbiology and Molecular Biology Reviews
Published
2003-09
Volume
67
Issue
3
Pages
400-428
ISSN
  • 1092-2172 (ISSN-L)
  • 1098-5557
OpenAlex
W2137959581
Cited by
1,179
References
263
Citations by year
2026: 44 · 2025: 56 · 2024: 65 · 2023: 45 · 2022: 61 · 2021: 65 · 2020: 53 · 2019: 60 · 2018: 55 · 2017: 58 · 2016: 58 · 2015: 62 · 2014: 82 · 2013: 57 · 2012: 56
FWCI
3.73
Type
journal article
Language
en
Open access
Locations
  • Microbiology and Molecular Biology Reviews (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Research Portal (King's College London) (submittedVersion)
Topics
  • Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
  • Health Sciences › Medicine › Epidemiology › Fungal Infections and Studies
Keywords
Candida albicans, secreted aspartyl proteinases, fungal virulence, pathogenesis, extracellular proteolysis, substrate specificity, immune evasion, tissue invasion, host-pathogen interaction
MeSH terms
Candida albicans, Candidiasis, Fungal Proteins, Humans, Virulence, Aspartic Acid Endopeptidases

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