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Expression of the Candida albicans Gene ALS1 in Saccharomyces cerevisiae Induces Adherence to Endothelial and Epithelial Cells
Open accessAbstract
To identify genes encoding adhesins that mediate the binding of Candida albicans to endothelial cells, a genomic library from this organism was constructed and used to transform Saccharomyces cerevisiae . These transformed organisms were screened for adherence to endothelial cells, and a highly adherent clone was identified. The adherence of this clone to endothelial cells was over 100-fold greater than that of control S. cerevisiae transformed with the empty plasmid. This clone also exhibited enhanced adherence to epithelial cells. The C. albicans gene contained within this clone was found to be ALS1 . These results indicate that ALS1 may encode a candidal adhesin.
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“even though previous studies have clearly demonstrated that Als1 is an adhesin [36,37].”
From Als3 Is a Candida albicans Invasin That Binds to Cadherins and Induces Endocytosis by Host Cells (2007) · cites this paper as [37]
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“Downloaded from www.microbiologyresearch.org by IP: 54.70.40.11 On: Wed, 05 Dec 2018 12:28:50 ofC. albicans INT1 (Gale et al., 1998),ALS1 (Fu et al., 1998b), ALA1 (Gaur & Klotz, 1997) or CAD1/AAF1 (Fu et al., 1998a) genes in S. cerevisiae is sufficient to direct the adhesion of this normally…”
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“ALA1 and ALS1 were identified based on their abilities to confer upon Saccharomyces cerevisiae the capacity to adhere to extracellular matrix proteins or human umbilical vein endothelial cells (11, 18).”
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“…of several of the Als proteins have been characterized – for example,Als1,Als3 andAls5 have been found to adhere, to varying degrees, to both epithelial and endothelial cell types, as well as to extracellular matrix proteins (Gaur and Klotz, 1997; Fu et al., 1998; Sheppard et al., 2004).”
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“The complete sequences of three members of the gene family, ALA1, ALS1, and ALS3, have been reported, but only ALA1 and ALS1 have been functionally characterized (6, 9).”
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“albicans ALS1 (agglutinin-like sequence) gene encodes an adhesin that mediates attachment to endothelial cells (4, 9).”
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“Agglutinin-like sequence (ALS) genes encoded cell-surface glycoproteins have important roles in the adherence to host surfaces,(10) such as agglutinin-like sequence 1 (Als1), which is capable of the inducing adherence to endothelial and epithelial cells.(11,12) Although the major protein of the hyphal cell wall hyphal…”
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“Als3 is able to bind extracellular matrix (ECM) proteins, epithelial and endothelial cells (Fu et al., 1998; Sheppard et al., 2004; Zhao et al., 2004; Liu & Filler, 2011), induce endocytosis via adherence to E- or Ncadherins (Phan et al.”
BackgroundA Genetic Code Alteration Is a Phenotype Diversity Generator in the Human Pathogen Candida albicans
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BackgroundPathogen interactions with endothelial cells and the induction of innate and adaptive immunity
Konradt, C., & Hunter, C. A. (2018) · European Journal of Immunology · doi:10.1002/eji.201646789 · Cited by 54
Zhao, H. F., Shen, Z., Kahn, P. C., & Lipke, P. N. (2001) · Journal of Bacteriology · doi:10.1128/jb.183.9.2874-2880.2001 · Cited by 53
Integrin-like proteins in Candida spp. and other microorganisms.
Hostetter, M. K. (1999) · Fungal Genetics and Biology · doi:10.1006/fgbi.1999.1165 · Cited by 55
C. albicans Colonization of Human Mucosal Surfaces
Southern, P. J., Horbul, J., Maher, D. M., & Davis, D. A. (2008) · PLoS ONE · doi:10.1371/journal.pone.0002067 · Cited by 48
“Candida-epithelial cell interactions using immortalized human epithelial cell lines in tissue culture [13,14,15].”
BackgroundAdhesins in the virulence of opportunistic fungal pathogens of human
Kumari, A., Tripathi, A. H., Gautam, P., Gahtori, R., Pande, A., Singh, Y. P., Madan, T., & Upadhyay, S. K. (2021) · Mycology: An International Journal on Fungal Biology · doi:10.1080/21501203.2021.1934176 · Cited by 49
“Among these proteins, Als1p (Buurman et al. 1998) and Ala1p (Gaur et al. 1999), also called Als5p (Fu et al. 1998) encoded by members of a large family of ALS genes (agglutinin-like sequence) (Hoyer 2001), have been investigated to have binding affinity for ECM proteins and components of endothelial and epithelial cel…”
BackgroundInfluentialZhao, X., Oh, S.-H., & Hoyer, L. L. (2007) · Microbiology · doi:10.1099/mic.0.2006/005017-0 · Cited by 46
“cerevisiae supported this hypothesis (Gaur & Klotz, 1997; Fu et al., 1998).”
BackgroundVaccines in the treatment of invasive candidiasis
Wang, X., Sui, X., Yan, L., Wang, Y., Cao, Y., & Jiang, Y. (2015) · Virulence · doi:10.4161/21505594.2014.983015 · Cited by 47
Saliva Promotes Candida albicans Adherence to Human Epithelial Cells
Holmes, A. R., Bandara, B. M. K., & Cannon, R. D. (2002) · Journal of Dental Research · doi:10.1177/002203450208100107 · Cited by 45
Gaur, N., Smith, R., & Klotz, S. (2002) · Cell Communication & Adhesion · doi:10.1080/15419060212187 · Cited by 46
“These studies have identified two specificity determinants for target recognition: (1) Ala1/Als5p recognizes only certain amino acids, threonine, serine, and alanine; and (2) these amino acids need to be localized in a region that is accessible to Ala1/Als5p; specifically, the amino acids must be localized in the free…”
BackgroundLamarre, C., Deslauriers, N., & Bourbonnais, Y. (2000) · Molecular Microbiology · doi:10.1046/j.1365-2958.2000.01715.x · Cited by 46
“Until now, molecular genetic approaches have identi®ed a few genes encoding hyphae-speci®c surface proteins that may contribute to differences in cell wall structure and functions (Hoyer et al., 1995; Bailey et al., 1996; Staab et al., 1996; Fu et al., 1998).”
BackgroundGlee, P. M., Cutler, J. E., Benson, E. E., Bargatze, R. F., & Hazen, K. C. (2001) · Infection and Immunity · doi:10.1128/iai.69.5.2815-2820.2001 · Cited by 42
“cells, epithelial cells, and ECM proteins (18, 19); ECM-binding”
BackgroundSecreted Proteinases and Other Virulence Mechanisms of Candida albicans
Monod, M., & Zepelin, M. B. (2002) · KARGER eBooks · doi:10.1159/000058865 · Cited by 44
Detection of Als Proteins on the Cell Wall of Candida albicans in Murine Tissues
Hoyer, L. L., Clevenger, J., Hecht, J. E., Ehrhart, E. J., & Poulet, F. M. (1999) · Infection and Immunity · doi:10.1128/iai.67.8.4251-4255.1999 · Cited by 41
Lagree, K., & Mitchell, A. P. (2017) · Microbiology Spectrum · doi:10.1128/microbiolspec.funk-0024-2016 · Cited by 41
“The S. cerevisiae cells expressing these proteins attached and formed bio-fi lms on abiotic and cellular substrates, albeit to varying degrees (30 – 32).”
BackgroundMolecular Genetic and Genomic Approaches to the Study of Medically Important Fungi
Magee, P. T., Gale, C. A., Berman, J. G., & Davis, D. A. (2003) · Infection and Immunity · doi:10.1128/iai.71.5.2299-2309.2003 · Cited by 42
“cerevisiae cells adhere to human cells (40, 42, 43, 46).”
BackgroundNiche-Specific Requirement for Hyphal Wall protein 1 in Virulence of Candida albicans
Staab, J. F., Datta, K., & Rhee, P. (2013) · PLoS ONE · doi:10.1371/journal.pone.0080842 · Cited by 44
“albicans to oral epithelial cells [2–6].”
Adhesion and Adhesives of Fungi and Oomycetes
Epstein, L., & Nicholson, R. L. (2016) · Springer eBooks · doi:10.1007/978-3-319-46082-6_2 · Cited by 44
The molecular basis of sex: linking yeast to human.
Swanson, W., Aagaard, J., Vacquier, V., Monné, M., Hosseini, H. S. A., & Jovine, L. (2011) · Molecular biology and evolution · doi:10.1093/molbev/msr026 · Cited by 42
“Moreover, specific adherence of Candida to human endothelial and epithelial cells requires Als1p Ig III amino acids centered around V285 (Fu et al. 1998; Loza et al. 2004; Sheppard et al. 2004; Dranginis et al. 2007), a residue that is also predicted to be exposed on the same region of the ZP-N…”
BackgroundKuhn, D. M., & Vyas, V. K. (2012) · FEMS Yeast Research · doi:10.1111/j.1567-1364.2011.00785.x · Cited by 38
“albicans (Fu et al., 1998) and the Epa proteins from C.”
BackgroundInfluentialThe pathophysiology and treatment of Candida sepsis
Spellberg, B. J., & Edwards, J. E. (2002) · Current Infectious Disease Reports · doi:10.1007/s11908-002-0005-3 · Cited by 37
Self-citationSSD1 Is Integral to Host Defense Peptide Resistance in Candida albicans
Gank, K. D., Yeaman, M. R., Kojima, S., Yount, N. Y., Park, H., Edwards, J. E., Filler, S. G., & Fu, Y. (2008) · Eukaryotic Cell · doi:10.1128/ec.00402-07 · Cited by 37
“The SSD1 gene in C. albicans strain BWP17 was disrupted using a previously described PCR method (40).”
BackgroundMethodInfluentialSelf-citationComprehensive genetic analysis of adhesin proteins and their role in virulence ofCandida albicans
Rosiana, S., Zhang, L., Kim, G. H., Revtovich, A. V., Uthayakumar, D., Sukumaran, A., Geddes‐McAlister, J., Kirienko, N. V., & Shapiro, R. S. (2021) · Genetics · doi:10.1093/genetics/iyab003 · Cited by 41
Identification of Streptococcus suis serotype 2 genes preferentially expressed in the natural host.
Li, W., Liu, L.-C., Qiu, D.-X., Chen, H.-C., & Zhou, R. (2010) · International Journal of Medical Microbiology · doi:10.1016/j.ijmm.2010.04.018 · Cited by 38
“ALS faciltated the adherence of C. albicans to extracelluar matrix proteins nd several endothelial and epithelial cell lines (Gaur and Klotz, 997; Fu et al., 1998).”
BackgroundGaur, N., & Klotz, S. (2004) · Microbiology · doi:10.1099/mic.0.26738-0 · Cited by 35
“At least two members of the ALS family, Als5p and Als1p, have been shown to confer upon Saccharomyces cerevisiae properties similar to that of C. albicans SRS adherence (Gaur & Klotz, 1997; Fu et al., 1998; Gaur et al., 1999).”
BackgroundBelanger, P. H., Johnston, D. A., Fratti, R. A., Zhang, M., & G. Filler, S. (2002) · Cellular Microbiology · doi:10.1046/j.1462-5822.2002.00232.x · Cited by 34
Self-citationAn Amyloid Core Sequence in the Major Candida albicans Adhesin Als1p Mediates Cell-Cell Adhesion
Ho, V., Herman‐Bausier, P., Shaw, C. E., Conrad, K. A., Garcia, M. C., Draghi, J. A., Dufrêne, Y. F., Lipke, P. N., & Rauceo, J. M. (2019) · mBio · doi:10.1128/mbio.01766-19 · Cited by 37
“albicans adhesin gene discovered, and when expressed in a Saccharomyces cerevisiae surface display model, it mediates formation of large aggregates and flocs, as well as binding to endothelial cells (6, 7).”
InfluentialLarge-scale gene function analysis in Candida albicans
Bruno, V. M., & Mitchell, A. P. (2004) · Trends in Microbiology · doi:10.1016/j.tim.2004.02.002 · Cited by 36
Li, F., & Palecek, S. P. (2005) · Biotechnology Progress · doi:10.1021/bp050236c · Cited by 32
Role of Aspergillus fumigatus DvrA in Host Cell Interactions and Virulence
Ejzykowicz, D. E., Solis, N. V., Gravelat, F. N., Chabot, J. C., Li, X., Sheppard, D. C., & Filler, S. G. (2010) · Eukaryotic Cell · doi:10.1128/ec.00055-10 · Cited by 30
“These proteins include Hwp1, Als1, and Als3 (11, 25, 39, 43).”
Self-citationCandidaSpecies Adhesion to Oral Epithelium: Factors Involved and Experimental Methodology Used
Henriques, M., Azeredo, J., & Oliveira, R. (2006) · Critical Reviews in Microbiology · doi:10.1080/10408410601023524 · Cited by 32
Kanaguchi, N., Narisawa, N., Ito, T., Kinoshita, Y., Kusumoto, Y., Shinozuka, O., & Senpuku, H. (2012) · BMC Oral Health · doi:10.1186/1472-6831-12-36 · Cited by 30
Bencúrová, E., Mlynárčik, P., & Bhide, M. R. (2011) · FEMS Immunology & Medical Microbiology · doi:10.1111/j.1574-695x.2011.00867.x · Cited by 30
“Previously, it was demonstrated that expression of the agglutinin-like ALS1 protein is responsible for the adherence to HUVEC and epithelial cells (Fu et al., 1998).”
BackgroundIranzo, M. X. A., Aguado, C., Pallotti, C., Cañizares, J. V., & Mormeneo, S. (2002) · Research in Microbiology · doi:10.1016/s0923-2508(02)01307-4 · Cited by 28
Metadata
- Authors
- Fu, Y., Rieg, G., Fonzi, W. A., Belanger, P. H., Edwards, J. E., & Filler, S. G.
- Affiliations
- University of California, Los Angeles (US)
- <!--label omitted: 1-->St. John’s Cardiovascular Research Center, Division of Infectious Diseases, Department of Medicine, Harbor-UCLA Research and Education Institute, Torrance, California 905021;
- Georgetown University (US)
- Venue
- Infection and Immunity
- Publisher
- American Society for Microbiology
- Published
- 1998-04
- Volume
- 66
- Issue
- 4
- Pages
- 1783-1786
- ISSN
- 0019-9567 (ISSN-L)
- 1098-5522
- PMC
- PMC108121
- OpenAlex
- W1965039542
- Cited by
- 159
- References
- 12
- Citations by year
- 2025: 1 · 2023: 1 · 2022: 1 · 2021: 5 · 2020: 3 · 2019: 3 · 2018: 6 · 2017: 3 · 2016: 3 · 2015: 6 · 2014: 10 · 2013: 4 · 2012: 3
- FWCI
- 7.06
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Infection and Immunity (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Allergy and Infectious Diseases (P01 AI-37194, R29AI040636, R01AI019990, R01-AI19990, P01AI037194)
- National Center for Research Resources (M01RR000425)
- 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 › Infectious Diseases › Fungal Infections and Studies
- Keywords
- Candida albicans, adhesins, cell adhesion, endothelial cells, epithelial cells, yeast transformation, genomic library screening, fungal adhesion, host cell binding
- MeSH terms
- Adhesiveness, Candida albicans, Endothelium, Vascular, Epithelial Cells, Fungal Proteins, Genes, Fungal, Humans, Saccharomyces cerevisiae
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