Differential Expression of Candida albicans Secreted Aspartyl Proteinase and Phospholipase B Genes in Humans Correlates with Active Oral and Vaginal Infections
Abstract
The in vivo expression of Candida albicans secreted aspartyl proteinase (SAP1-SAP8) and phospholipase B (PLB1 and PLB2) genes was analyzed in 137 human subjects with oral and vaginal candidiasis or carriage. Total RNA was isolated from whole unstimulated saliva or vaginal swabs, and the expression of SAP1-8 and PLB1-2 was evaluated by reverse-transcriptase polymerase chain reaction using specific primer sets. A spectrum of SAP gene expression profiles was obtained from different C. albicans strains during symptomatic disease and asymptomatic carriage. SAP2 and SAP5 were the most common genes expressed during both infection and carriage. SAP1, SAP3, SAP4, SAP7, SAP8, and PLB1 expression was correlated with oral disease, whereas SAP1, SAP3, and SAP6-SAP8 expression was correlated with vaginal disease. Furthermore, SAP1, SAP3, and SAP8 were preferentially expressed in vaginal, rather than oral, infections. This study demonstrates the differential expression of the hydrolytic enzyme genes in humans and correlates the expression of specific Candida species virulence genes with active disease and anatomical location.
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C. albicans employs phospholipases and proteases for nutrient acquisition, and amino acid permeases and transporters for additional nutrient uptake.
“phospholipases and proteases for nutrient acquisition, and amino acid permeases and transporters for additional nutrient uptake (39).”
From <i>Candida auris</i> metabolism and growth preferences in physiologically relevant skin-like conditions (2026) · cites this paper as [39]
Cites
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“To gain insight into the relationship between HWP1 gene expression and commensalism or symptomatic tissue invasion, we analysed the same carrier and candidiasis specimens that had been used previously to determine SAP and PLB gene expression in samples of whole unstimulated saliva and vaginal swabs (Naglik et al., 200…”
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“The strongest response was previously observed for Sap4 and Sap6, which are dominant for the filamentous form of C. albicans (Hube et al., 1994; Naglik et al., 2003a) which is more virulent than the unicellular yeastlike form and induces a stronger NET response upon contact with neutrophils.”
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Secreted Aspartic Proteinases: Key Factors in Candida Infections and Host-Pathogen Interactions
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“This post-endocytic step is likely the secretion of lytic enzymes by the organism such as secreted aspartyl proteinases, phospholipases and lipases (Ibrahim et al., 1998; Naglik et al., 2003; Schofield et al., 2003; Stehr et al., 2004).”
BackgroundAnticandidal Immunity and Vaginitis: Novel Opportunities for Immune Intervention
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“showed that 40% (32/80) of oral infection isolates exhibited SAP6 expression as opposed to 29% (20/69) of carrier isolates [36].”
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“[23,24] also showed that some of these virulence factors are expressed preferentially in patients with candidiasis, rather than asymptomatic Candida carriers.”
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“In this work, to analyse the expression patterns of ALS1–ALS3, HWP1, SAP1, SAP4–SAP6, LIP1–LIP10, PLB1-PLB2, CDR1, and MDR1, we implemented an in vitromodel of infection of human vaginal cells with C. albicans strains isolated from women with VVC. Hindawi Publishing Corporation Canadian Journal of…”
BackgroundInfluentialComparative Analysis of the Capacity of the Candida Species To Elicit Vaginal Immunopathology
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Barros, P. P., Ribeiro, F. C., Rossoni, R. D., Junqueira, J. C., & Jorge, A. O. (2016) · Archives of Oral Biology · doi:10.1016/j.archoralbio.2016.01.005 · Cited by 45 · see citing works
“The primers for all genes analyzed in the present study were described and used in the same way as indicated by Nailis, Coenye, Van Nieuwerburgh, Deforce, and Nelis (2006) and Nailis et al. (2010) and Hnisz, Bardet, Nobile, Petryshyn, and Glaser (2012).”
BackgroundMethodInfluentialBassyouni, R., Wegdan, A., Abdelmoneim, A., Said, W., & Aboelnaga, F. (2015) · Journal of Microbiology and Biotechnology · doi:10.4014/jmb.1504.04009 · Cited by 45 · see citing works
Role of Candida albicans-Secreted Aspartyl Proteinases (Saps) in Severe Early Childhood Caries
Li, W., Yu, D.-S., Gao, S., Lin, J., Chen, Z., & Zhao, W. (2014) · International Journal of Molecular Sciences · doi:10.3390/ijms150610766 · Cited by 45 · see citing works
“[14], samples were obtained from individuals with, or carrying, oral and vaginal candidiasis, and the expression of Sap1–Sap8 was evaluated in an in vivo model.”
BackgroundTaylor, B., Hannemann, H., Sehnal, M., Biesemeier, A., Schweizer, A., Röllinghoff, M., & Schröppel, K. (2005) · Infection and Immunity · doi:10.1128/iai.73.10.7061-7063.2005 · Cited by 44 · see citing works
“Although the observed up-regulation of SAP7 is a consequence of this type of superficial infection (20, 25), it could well be that C.”
Niche-Specific Requirement for Hyphal Wall protein 1 in Virulence of Candida albicans
Staab, J., Datta, K., & Rhee, P. (2013) · PLoS ONE · doi:10.1371/journal.pone.0080842 · Cited by 42 · see citing works
Barrier Activity in <i>Candida albicans</i> Mediates Pheromone Degradation and Promotes Mating
Schaefer, D., Côte, P., Whiteway, M., & Bennett, R. J. (2007) · Eukaryotic Cell · doi:10.1128/ec.00090-07 · Cited by 40 · see citing works
“For the PCR experiments, oligonucleotides were chosen to specifically amplify each target gene, as previously described (7, 39, 51).”
MethodAntimicrobial photodynamic therapy reduces gene expression of Candida albicans in biofilms
Jordão, C. C., de Sousa, T. V., Klein, M. I., Dias, L. M., Pavarina, A. C., & Carmello, J. C. (2020) · Photodiagnosis and Photodynamic Therapy · doi:10.1016/j.pdpdt.2020.101825 · Cited by 43 · see citing works
Targeting Virulence Factors of Candida albicans with Natural Products
Bu, Q., Bao, M.-Y., Yang, Y., Wang, T.-M., & Wang, C. (2022) · Foods · doi:10.3390/foods11192951 · Cited by 46 · see citing works
Tavanti, A., Pardini, G., Campa, D., Davini, P., Lupetti, A., & Senesi, S. (2004) · Journal of Clinical Microbiology · doi:10.1128/jcm.42.10.4726-4734.2004 · Cited by 38 · see citing works
“All SAP1-10 genes were expressed by all of the commensal b and c strains analyzed (see below), including the SAP7 gene, whose expression has so far been detected only in vivo (13, 25, 26, 27).”
BackgroundInfluentialAdhesins in the virulence of opportunistic fungal pathogens of human
Kumari, A., Tripathi, A. H., Gautam, P., Gahtori, R., Pande, A., Singh, Y., Madan, T., & Upadhyay, S. (2021) · Mycology · doi:10.1080/21501203.2021.1934176 · Cited by 37 · see citing works
“albicans virulence factors may also vary during different stages of infection (localised and systemic), and host immune response (Naglik et al. 2003).”
BackgroundCastillo, G. D. V., de Blanc, S. L. D., Sotomayor, C., & Azcurra, A. (2018) · Archives of Oral Biology · doi:10.1016/j.archoralbio.2018.02.012 · Cited by 36 · see citing works
de Bernardis, F., Tacconelli, E., Mondello, F., Cataldo, A., Arancia, S., Cauda, R., & Cassone, A. (2004) · FEMS Immunology & Medical Microbiology · doi:10.1016/j.femsim.2003.12.006 · Cited by 36 · see citing works
Bocheńska, O., Rapała-Kozik, M., Wolak, N., Aoki, W., Ueda, M., & Kozik, A. (2016) · Acta Biochimica Polonica · doi:10.18388/abp.2016_1318 · Cited by 34 · see citing works
“Considering the proteases which were hereby found to degrade His5, SAP1, SAP2, SAP4, SAP7 and SAP8 genes are expressed at a significant level during oral infections (Naglik et al., 2003b).”
BackgroundInfluentialSvobodová, E., Staib, P., Losse, J., Hennicke, F., Barz, D., & Józsi, M. (2012) · The Journal of Immunology · doi:10.4049/jimmunol.1200185 · Cited by 33 · see citing works
“Key virulence factors of Candida include the ability to switch between yeast and hypha morphology enabling the fungus in its spreading and invasion of the human host (50, 63), the production of enzymes such as secreted aspartyl proteases and phospholipases (64), and the expression of adhesins (65).”
Gupta, G., Jain, R., Maikhuri, J. P., Shukla, P., Kumar, M., Roy, A., Patra, A., Singh, V. P., & Batra, S. (2005) · Human Reproduction · doi:10.1093/humrep/dei041 · Cited by 33 · see citing works
“Candida albicans is the most commonly encountered fungal pathogen of the human vagina ( Naglik et al., 2003 ).”
BackgroundLarge-Scale Chromosomal Changes and Associated Fitness Consequences in Pathogenic Fungi
Forche, A. (2014) · Current Fungal Infection Reports · doi:10.1007/s12281-014-0181-2 · Cited by 30 · see citing works
A quest to find good primers for gene expression analysis of Candida albicans from clinical samples.
Alonso, G., Pavarina, A. C., Sousa, T., & Klein, M. (2018) · Journal of Microbiological Methods · doi:10.1016/j.mimet.2018.02.010 · Cited by 30 · see citing works
“…eight newly designed primers (ACT1, HWP1, ALS1, LIP3, CAT1, CAP1, EFG1 and PLB1) and three published primers (HWP1 by Alves et al., 2014, SAP1 by Naglik et al., 2003b, and SOD1 by Zhu et al., 2011) were standardized and under the conditions described, are suitable for use in clinical studies.”
InfluentialNaglik, J. R. (2014) · New Journal of Science · doi:10.1155/2014/390241 · Cited by 29 · see citing works
Self-citation“Under Pressure” – How fungi evade, exploit, and modulate cells of the innate immune system
Lange, T., Kasper, L., Gresnigt, M., Brunke, S., & Hube, B. (2023) · Seminars in Immunology · doi:10.1016/j.smim.2023.101738 · Cited by 29 · see citing works
Integrating Inflammasome Signaling in Sexually Transmitted Infections
Lupfer, C. R., & Anand, P. (2016) · Trends in Immunology · doi:10.1016/j.it.2016.08.004 · Cited by 24 · see citing works
Badrane, H., Cheng, S.-J., Nguyen, M., Jia, H., Zhang, Z.-D., Weisner, N., & Clancy, C. (2005) · Microbiology · doi:10.1099/mic.0.27998-0 · Cited by 28 · see citing works
“…members of the SAP family of secreted aspartyl proteases and genes encoding phospholipases are also regulated at the transcriptional level in vivo, with expression patterns varying depending on tissue sites and stages of infection (Staib et al., 2000a; Fradin et al., 2003; Naglik et al., 2003).”
BackgroundPadder, S. A., Ramzan, A., Tahir, I., Rehman, R. U., & Shah, A. H. (2022) · Critical Reviews in Microbiology · doi:10.1080/1040841x.2021.1935447 · Cited by 27 · see citing works
Salivary pellicles equalise surfaces’ charges and modulate the virulence of Candida albicans biofilm
Cavalcanti, Y. W., Wilson, M. J., Lewis, M. A. O., Williams, D. W., Senna, P. M., Cury, A. A. D. B., & da Silva, W. J. (2016) · Archives of Oral Biology · doi:10.1016/j.archoralbio.2016.02.016 · Cited by 28 · see citing works
“…(Alves et al., 2014; Dongari-Bagtzoglou et al., 2009; Malic et al., 2007); to produce and secrete proteolytic enzymes (Custodio, Silva, Paes Leme, Cury, & Del Bel Cury, 2014; Naglik et al., 2008; Naglik et al., 2003); and to evade host immune responses (Wei, Rogers, Lewis, & Williams, 2011).”
BackgroundBras, G., Bocheńska, O., Rapała-Kozik, M., Guevara-Lora, I., Faussner, A., & Kozik, A. (2012) · Biological chemistry · doi:10.1515/hsz-2012-0157 · Cited by 27 · see citing works
“These may include other C. albicans SAPs with more neutral pH optima, such as the SAP4-6 subset (Naglik et al. , 2003a ), or serineor metalloproteinases that occasionally have been reported to occur in this yeast species (Rodier et al. , 1999 ; dos Santos et al. , 2006 ).”
BackgroundMethodMardegan, R. D. C., Foglio, M., Gonçalves, R., & Höfling, J. (2006) · LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) · doi:10.20396/bjos.v5i16.8641872 · Cited by 27 · see citing works
Russell, C., & Brown, A. J. (2005) · Fungal Genetics and Biology · doi:10.1016/j.fgb.2005.04.008 · Cited by 27 · see citing works
Kozik, A., Gogól, M., Bocheńska, O., Karkowska-Kuleta, J., Wolak, N., Kamysz, W., Aoki, W., Ueda, M., Faussner, A., & Rapała-Kozik, M. (2015) · BMC Microbiology · doi:10.1186/s12866-015-0394-8 · Cited by 24 · see citing works
“This subject has been extensively reviewed [25,35], but only a few representative findings can be cited here.”
BackgroundResultAntony, G., Saralaya, V., Bhat, K. G., Shenoy, M., & Shivananda, P. (2009) · Revista Iberoamericana de Micologia · doi:10.1016/j.riam.2009.03.001 · Cited by 24 · see citing works
- Authors
- Naglik, J. R., Rodgers, C. A., Shirlaw, P. J., Dobbie, J. L., Fernandes‐Naglik, L. L., Greenspan, D., Agabian, N., & Challacombe, S. J.
- Affiliations
- King's College London (GB)
- Guy's Hospital (GB)
- University of California, San Francisco (US)
- Corresponding author
- Naglik, Julian R.
- Venue
- The Journal of Infectious Diseases
- Publisher
- Oxford University Press (OUP)
- Published
- 2003-08
- Volume
- 188
- Issue
- 3
- Pages
- 469-479
- ISSN
- 0022-1899 (ISSN-L)
- 1537-6613
- OpenAlex
- W2108569205
- Cited by
- 206
- References
- 0
- Citations by year
- 2026: 3 · 2025: 15 · 2024: 5 · 2023: 6 · 2022: 6 · 2021: 13 · 2020: 8 · 2019: 11 · 2018: 8 · 2017: 9 · 2016: 14 · 2015: 8 · 2014: 10 · 2013: 7 · 2012: 11
- FWCI
- 5.63
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Infectious Diseases (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (King's College London) (submittedVersion)
- Funders
- National Institutes of Health (5r01ai033317-08)
- National Institute of Allergy and Infectious Diseases (AI33317)
- National Institute of Dental and Craniofacial Research (P01 DE07946, P01DE007946)
- 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, phospholipase B, gene expression, oral candidiasis, vaginal candidiasis, asymptomatic carriage, virulence genes, hydrolytic enzymes, saliva, vaginal swabs
- MeSH terms
- Candida albicans, Candidiasis, Oral, Candidiasis, Vulvovaginal, Carrier State, Female, Fungal Proteins, Humans, Lysophospholipase, Male, Middle Aged, Saliva, Vagina, Gene Expression, Aspartic Acid Endopeptidases, DNA Primers, Reverse Transcriptase Polymerase Chain Reaction
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