The DOI matches its Crossref record; 56 of the 59 references it cites were found in a registry or an index.
Functional and Structural Diversity in the Als Protein Family of Candida albicans
Open accessAbstract
The human fungal pathogen Candida albicans colonizes and invades a wide range of host tissues. Adherence to host constituents plays an important role in this process. Two members of the C. albicans Als protein family (Als1p and Als5p) have been found to mediate adherence; however, the functions of other members of this family are unknown. In this study, members of the ALS gene family were cloned and expressed in Saccharomyces cerevisiae to characterize their individual functions. Distinct Als proteins conferred distinct adherence profiles to diverse host substrates. Using chimeric Als5p-Als6p constructs, the regions mediating substrate-specific adherence were localized to the N-terminal domains in Als proteins. Interestingly, a subset of Als proteins also mediated endothelial cell invasion, a previously unknown function of this family. Consistent with these results, homology modeling revealed that Als members contain anti-parallel beta-sheet motifs interposed by extended regions, homologous to adhesins or invasins of the immunoglobulin superfamily. This finding was confirmed using circular dichroism and Fourier transform infrared spectrometric analysis of the N-terminal domain of Als1p. Specific regions of amino acid hypervariability were found among the N-terminal domains of Als proteins, and energy-based models predicted similarities and differences in the N-terminal domains that probably govern the diverse function of Als family members. Collectively, these results indicate that the structural and functional diversity within the Als family provides C. albicans with an array of cell wall proteins capable of recognizing and interacting with a wide range of host constituents during infection.
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In the citing paper
“This gene family encodes eight GPI-linked cell surface proteins that mediate binding to diverse host substrates [20][21][22][23][24][25].”
From Als3 Is a Candida albicans Invasin That Binds to Cadherins and Induces Endocytosis by Host Cells (2007) · cites this paper as [23]
In the citing paper
“We found that Saccharomyces cerevisiae expressing Als3 were avidly endocytosed by endothelial cells.”
From Als3 Is a Candida albicans Invasin That Binds to Cadherins and Induces Endocytosis by Host Cells (2007) · cites this paper as [23]
In the citing paper
“Also, we found that S. cerevisiae expressing Als3 bound to both endothelial cells and FaDu oral epithelial cells [23].”
From Als3 Is a Candida albicans Invasin That Binds to Cadherins and Induces Endocytosis by Host Cells (2007) · cites this paper as [23]
In the citing paper
“Similar experiments suggested that Als1 and Als5 could also induce endocytosis, although with considerably less efficiency than Als3 [23].”
From Als3 Is a Candida albicans Invasin That Binds to Cadherins and Induces Endocytosis by Host Cells (2007) · cites this paper as [23]
In the citing paper
“The N-terminal domain contains the substratebinding region [23,26].”
From Als3 Is a Candida albicans Invasin That Binds to Cadherins and Induces Endocytosis by Host Cells (2007) · cites this paper as [23]
In the citing paper
“Computer-assisted modeling of the N-termini of Als1, Als3, and Als5 predicts the presence of antiparallel b sheets that define the immunoglobulin superfamily [23].”
From Als3 Is a Candida albicans Invasin That Binds to Cadherins and Induces Endocytosis by Host Cells (2007) · cites this paper as [23]
In the citing paper
“Previously, we determined that the N-terminal region of Als proteins contains the substrate-binding site [23,26].”
From Als3 Is a Candida albicans Invasin That Binds to Cadherins and Induces Endocytosis by Host Cells (2007) · cites this paper as [23]
In the citing paper
“The Als family of proteins contains six members in addition to Als1 and Als3 [20][21][22][23][24][25].”
From Als3 Is a Candida albicans Invasin That Binds to Cadherins and Induces Endocytosis by Host Cells (2007) · cites this paper as [23]
In the citing paper
“When expressed in S. cerevisiae, Als5 induces weak endothelial cell endocytosis similar to that induced by Als1 [23].”
From Als3 Is a Candida albicans Invasin That Binds to Cadherins and Induces Endocytosis by Host Cells (2007) · cites this paper as [23]
In the citing paper
“Previously, we have reported that S. cerevisiae expressing Als1 or Als3 binds to a variety of host constituents, including endothelial cells, epithelial cells, laminin, and fibronectin [23].”
From Als3 Is a Candida albicans Invasin That Binds to Cadherins and Induces Endocytosis by Host Cells (2007) · cites this paper as [23]
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“cerevisiae promotes binding to several different protein-coated substrate”
Als3 Is a Candida albicans Invasin That Binds to Cadherins and Induces Endocytosis by Host Cells
Phan, Q. T., Myers, C. L., Fu, Y., Sheppard, D. C., Yeaman, M. R., Welch, W. H., Ibrahim, A. S., Edwards, J. E., & Filler, S. G. (2007) · PLoS Biology · doi:10.1371/journal.pbio.0050064 · Cited by 641
“cerevisiae expressing Als3 are endocytosed by endothelial cells [23].”
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Verstrepen, K. J., & Klis, F. M. (2006) · Molecular Microbiology · doi:10.1111/j.1365-2958.2006.05072.x · Cited by 589
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Nobile, C. J., Andes, D. R., Nett, J. E., Smith, F. J., Yue, F., Phan, Q.-T., Edwards, J. E., Filler, S. G., & Mitchell, A. P. (2006) · PLoS Pathogens · doi:10.1371/journal.ppat.0020063 · Cited by 507
“This close relationship is reflected by their similar substrate binding properties [29].”
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“endothelial cells and subendothelial matrix proteins) and medically relevant plastics [54,55].”
BackgroundSelf-citationThe Antifungal Pipeline: Fosmanogepix, Ibrexafungerp, Olorofim, Opelconazole, and Rezafungin
Hoenigl, M., Sprute, R., Egger, M., Arastehfar, A., Cornely, O. A., Krause, R., Lass-Flörl, C., Prattes, J., Spec, A., Thompson, G. R., et al. (2021) · Drugs · doi:10.1007/s40265-021-01611-0 · Cited by 467
Function of Candida albicans Adhesin Hwp1 in Biofilm Formation
Nobile, C. J., Nett, J. E., Andes, D. R., & Mitchell, A. P. (2006) · Eukaryotic Cell · doi:10.1128/ec.00194-06 · Cited by 395
“It is possible that the distinction between null mutant phenotypes is not an accurate reflection of protein function because other Als family members may compensate for the absence of Als3 under some conditions (16, 22).”
BackgroundMolecular organization of the cell wall of Candida albicans and its relation to pathogenicity
Ruiz-Herrera, J., Victoria Elorza, M., ValentÃn, E., & Sentandreu, R. (2006) · FEMS Yeast Research · doi:10.1111/j.1567-1364.2005.00017.x · Cited by 376
Hoyer, L. L., Green, C. B., Oh, S.-H., & Zhao, X. (2008) · Medical Mycology · doi:10.1080/13693780701435317 · Cited by 356
Candida albicans Als3, a multifunctional adhesin and invasin
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“Als3, like Als1 and Als5, has broad substrate specificity and thus mediates adherence to a variety of host constituents (55).”
BackgroundInfluentialSelf-citationComplementary Adhesin Function in C. albicans Biofilm Formation
Nobile, C. J., Schneider, H. A., Nett, J. E., Sheppard, D. C., Filler, S. G., Andes, D. R., & Mitchell, A. P. (2008) · Current Biology · doi:10.1016/j.cub.2008.06.034 · Cited by 351
“To complement the als1/als1 als3/als3 double mutant with a wild-type copy of ALS1 or ALS3, a full–length version of ALS1 or ALS3 was digested from pGEMT-Easy with PvuI and SphI [22], and then subcloned into pDS10 for ALS1 or pDS11 for ALS3 [37].”
InfluentialSelf-citationThe evolution of drug resistance in clinical isolates of Candida albicans.
Ford, C. B., Funt, J. M., Abbey, D., Issi, L., Guiducci, C., Martinez, D. A., Delorey, T., Li, B. Y., White, T. C., Cuomo, C., et al. (2015) · eLife · doi:10.7554/elife.00662 · Cited by 348
“Other mutations were in genes not previously related to fluconazole resistance, including cell adhesion (ALS3,5 and 7 and HYR3; [Hoyer et al., 1998; Sheppard et al., 2004; Hoyer et al., 2008]), filamentous growth (FGR14, FGR28, and EFH, [Uhl et al., 2003; Connolly et al., 2013]), and biofilm formation (BCR1 and YAK1;…”
A Human-Curated Annotation of the Candida albicans Genome
Braun, B. R., van het Hoog, M., d'Enfert, C., Martchenko, M., Dungan, J., Kuo, A., Inglis, D. O., Uhl, M. A., Hogues, H., Berriman, M., et al. (2005) · PLoS Genetics · doi:10.1371/journal.pgen.0010001 · Cited by 342
“The ALS genes encode large cell-surface glycoproteins that function in host–pathogen interactions [50,51].”
BackgroundWang, C.-S., & Leger, R. S. (2007) · Eukaryotic Cell · doi:10.1128/ec.00409-06 · Cited by 337
“They share a similar 3-domain structure to the Candida albicans cell wall ALS 18 (Agglutinin-Like-Sequence) proteins (14, 27) that form rapid and extremely stable H-bond dependant 19 associations with host proteins and peptides (9).”
Almeida, R. S., Brunke, S., Albrecht, A., Thewes, S., Laue, M., Edwards, J. E., Filler, S. G., & Hube, B. (2008) · PLoS Pathogens · doi:10.1371/journal.ppat.1000217 · Cited by 330
“albicans ALS3 [77].”
Self-citationA collagenous protective coat enables Metarhizium anisopliae to evade insect immune responses.
Wang, C.-S., & Leger, R. S. (2006) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.0601951103 · Cited by 324
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de Groot, P. D., Ram, A., & Klis, F. (2005) · Fungal Genetics and Biology · doi:10.1016/j.fgb.2005.04.002 · Cited by 322
“…and non-sexual adhesion proteins such as the Xocculins in S. cerevisiae, the Als proteins in C. albicans, and the Epa proteins in C. glabrata (De Las Peñas et al., 2003; Hoyer, 2001; Klotz et al., 2004; Li and Palecek, 2003; Lipke and Kurjan, 1992; Sheppard et al., 2004; Verstrepen et al., 2003).”
BackgroundAdhesins in human fungal pathogens: glue with plenty of stick.
de Groot, P. W. J., Bader, O., de Boer, A. D., Weig, M., & Chauhan, N. (2013) · Eukaryotic Cell · doi:10.1128/ec.00364-12 · Cited by 319
A Biochemical Guide to Yeast Adhesins: Glycoproteins for Social and Antisocial Occasions
Dranginis, A. M., Rauceo, J. M., Coronado, J. E., & Lipke, P. N. (2007) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.00037-06 · Cited by 294
“Interestingly, the globular regions of the homologous Als proteins have been modeled more recently, and Ig-like templates were also used in that study (107).”
MethodFungal Invasion of Normally Non-Phagocytic Host Cells
Filler, S. G., & Sheppard, D. C. (2006) · PLoS Pathogens · doi:10.1371/journal.ppat.0020129 · Cited by 275
“Binding to these surface proteins induces the phosphorylation of at least two different endothelial cell proteins, which in turn causes the rearrangement of the endothelial cell microfilaments to produce pseudopods and initiate endocytosis [19,30,31,35].”
BackgroundSelf-citationLatgé, J. (2010) · Cellular Microbiology · doi:10.1111/j.1462-5822.2010.01474.x · Cited by 303
“This issue is especially complicated by the fact that the binding specificities vary with the different members of the family (Sheppard et al., 2004; Zupancic et al., 2008).”
BackgroundGenetics and genomics of Candida albicans biofilm formation
Nobile, C. J., & Mitchell, A. P. (2006) · Cellular Microbiology · doi:10.1111/j.1462-5822.2006.00761.x · Cited by 281
“Als family members are known to interact with several substrates, including host cells and proteins (Hoyer, 2001; Sundstrom, 2002; Sheppard et al., 2004; Kumamoto and Vinces, 2005).”
BackgroundA yeast by any other name: Candida glabrata and its interaction with the host
Kaur, R., Domergue, R., Zupancic, M. L., & Cormack, B. P. (2005) · Current Opinion in Microbiology · doi:10.1016/j.mib.2005.06.012 · Cited by 271
Candida glabrata: A review of its features and resistance
Rodrigues, C. F., Silva, S., & Henriques, M. (2014) · European Journal of Clinical Microbiology & Infectious Diseases · doi:10.1007/s10096-013-2009-3 · Cited by 268
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“This part contains multiple antiparallel β-sheet domains containing minor αhelical and β-turn components, which indicates that products of ALS genes are members of immunoglobulin family (Sheppard et al., 2004).”
BackgroundComparative genomics of the fungal pathogens Candida dubliniensis and Candida albicansPreprint
Jackson, A. P., Gamble, J. A., Yeomans, T., Moran, G. P., Saunders, D., Harris, D. E., Aslett, M. A., Barrell, J. F., Butler, G., Citiulo, F., et al. (2009) · Genome Research · doi:10.1101/gr.097501.109 · Cited by 220
“…Research 2231 www.genome.org for C. albicans, it does so less efficiently than C. albicans under a wide range of hypha-induction conditions (Stokes et al. 2007) and exhibited low levels of filamentation in infection model experiments (Vilela et al. 2002; Moran et al. 2007; Stokes et al. 2007).”
BackgroundHoefs, S., Mogavero, S., & Hube, B. (2016) · The Journal of Microbiology · doi:10.1007/s12275-016-5514-0 · Cited by 251
“The eight members that are encoded by the ALS gene family (ALS1-7 and ALS9) are cell surface proteins and are glycosylphosphatidylinositol (GPI)linked to the ß-1,6-glucans of the fungal cell wall (Gaur and Klotz, 1997; Hoyer, 2001; Sheppard et al., 2004).”
BackgroundInfluentialSchmidt, C. S., White, C. J., Ibrahim, A. S., Filler, S. G., Fu, Y., Yeaman, M. R., Edwards, J. E., & Hennessey, J. P. (2012) · Vaccine · doi:10.1016/j.vaccine.2012.10.038 · Cited by 233
“It also has both sequence and structural homology with cell surface proteins on Staphylococcus aureus [23].”
BackgroundSelf-citationInteractions of Candida albicans with epithelial cells
Zhu, W., & Filler, S. G. (2010) · Cellular Microbiology · doi:10.1111/j.1462-5822.2009.01412.x · Cited by 223
“Similar studies suggest that Als1 can also induce epithelial cell endocytosis, although with lower efficiency than Als3 (Sheppard et al., 2004; Phan et al., 2007).”
BackgroundResultInfluentialSelf-citationSilverman, R. J., Nobbs, A. H., Vickerman, M. M., Barbour, M. E., & Jenkinson, H. F. (2010) · Infection and Immunity · doi:10.1128/iai.00685-10 · Cited by 219
“heterologous ALS3 under the alcohol dehydrogenase (ADH) promoter (50).”
BackgroundOrigins of variation in the fungal cell surface
Verstrepen, K. J., Reynolds, T. B., & Fink, G. R. (2004) · Nature Reviews Microbiology · doi:10.1038/nrmicro927 · Cited by 204
Edwards, J. E., Schwartz, M. M., Schmidt, C. S., Sobel, J. D., Nyirjesy, P., Schodel, F., Marchus, E., Lizakowski, M., DeMontigny, E. A., Hoeg, J., et al. (2018) · Clinical Infectious Diseases · doi:10.1093/cid/ciy185 · Cited by 213
Self-citationPark, H., Myers, C. L., Sheppard, D. C., Phan, Q. T., Sanchez, A. A., E. Edwards, J., & Filler, S. G. (2004) · Cellular Microbiology · doi:10.1111/j.1462-5822.2004.00476.x · Cited by 207
“Efg1p is also known to regulate the expression of adhesins, such as Hwp1p, Als1p and Als3p that mediate the binding of C. albicans to oral epithelial cells (Sharkey et al., 1999; Braun and Johnson, 2000; Fu et al., 2002; Sheppard et al., 2004).”
BackgroundSelf-citationVillar, C. C., Kashleva, H., Nobile, C. J., Mitchell, A. P., & Dongari‐Bagtzoglou, A. I. (2007) · Infection and Immunity · doi:10.1128/iai.00054-07 · Cited by 215
“These mechanisms include expression of host recognition molecules or adhesins 28 (13, 40, 49), ability to exist in reversible morphotypes (5), undergo phenotypic switching 29 (29, 44), and expression of tissue invasion-facilitating enzymes, such as phospholipases 30 and secreted aspartyl proteinases (12, 15, 22, 32, 4…”
BackgroundHoyer, L. L., & Cota, E. (2016) · Frontiers in Microbiology · doi:10.3389/fmicb.2016.00280 · Cited by 229
“The NT domain was implicated in much of the inferred protein– protein interactions (Loza et al., 2004; Sheppard et al., 2004; Zhao et al., 2006).”
BackgroundMethodInfluentialTorosantucci, A., Chiani, P., Bromuro, C., Bernardis, F. D., Palma, A. S., Liu, Y., Mignogna, G., Maras, B., Colone, M., Stringaro, A., et al. (2009) · PLoS ONE · doi:10.1371/journal.pone.0005392 · Cited by 211
Candida albicans Als3p is required for wild-type biofilm formation on silicone elastomer surfaces
Zhao, X., Daniels, K. J., Oh, S.-H., Green, C. B., Yeater, K. M., Soll, D. R., & Hoyer, L. L. (2006) · Microbiology · doi:10.1099/mic.0.28959-0 · Cited by 179
“Another study claimed to demonstrate adhesive specificity within the N-terminal domain of Als5p and Als6p using a domainswapping approach (Sheppard et al., 2004).”
Spellberg, B. J., Ibrahim, A. S., Avanesian, V., Fu, Y., Myers, C., Phan, Q. T., Filler, S. G., Yeaman, M. R., & Edwards, Jr. (2006) · The Journal of Infectious Diseases · doi:10.1086/504691 · Cited by 180
“When compared with one another, Als1p mediates greater adherence to endothelial cells and gelatin but inferior adherence to epithelial cells [6].”
BackgroundInfluentialSelf-citationCandida albicans-epithelial interactions and pathogenicity mechanisms: scratching the surface
Moyes, D. L., Richardson, J. P., & Naglik, J. R. (2015) · Virulence · doi:10.1080/21505594.2015.1012981 · Cited by 197
“cerevisiae over-expression mutants showing increased adherence.(26,31) As well as Hwp1p and Als family proteins, other adhesins have been identified.”
BackgroundWatanabe, N.-A., Miyazaki, M., Horii, T., Sagane, K., Tsukahara, K., & Hata, K. (2012) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00731-11 · Cited by 169
“albicans (15, 55), GPI biosynthesis inhibition is expected to lead to the suppression of hyphal growth and reduce adherence of C.”
BackgroundZhao, X.-M., Oh, S.-H., Yeater, K., & Hoyer, L. (2005) · Microbiology · doi:10.1099/mic.0.27763-0 · Cited by 166
“Overproduction of other Als proteins in Saccharomyces cerevisiae produced an adherent phenotype for this normally non-adherent organism, suggesting they may also play a role in C. albicans adhesion (Gaur & Klotz, 1997; Sheppard et al., 2004).”
BackgroundCovalently linked cell wall proteins of Candida albicans and their role in fitness and virulence
Klis, F. M., Sosinska, G. J., de Groot, P. W. J., & Brul, S. (2009) · FEMS Yeast Research · doi:10.1111/j.1567-1364.2009.00541.x · Cited by 165
“…with green fluorescent protein tagging: Pga59 and 62), by immunogold-labeling (Sap 9 and Sap10), or by expression cloning in S. cerevisiae and binding of the transformed cells to antibody- or ligand-coated magnetic beads (the Als protein family, Csa1; Lamarre et al., 2000; Sheppard et al., 2004).”
BackgroundMethodInfluentialKean, R., Rajendran, R., Haggarty, J. H., Townsend, E. R., Short, B., Burgess, K. E., Lang, S., Millington, O. R., Mackay, W. G., Williams, C., et al. (2017) · Frontiers in Microbiology · doi:10.3389/fmicb.2017.00258 · Cited by 216
“Als3p shares between 80 and ≥95% homology with collagen binding and clumping factor proteins of S. aureus (Sheppard et al., 2004), therefore the cellular basis for these interactions may be reciprocal.”
BackgroundComprehensive Analysis of Glycosylphosphatidylinositol-Anchored Proteins in Candida albicans
Richard, M. L., & Plaine, A. (2007) · Eukaryotic Cell · doi:10.1128/ec.00297-06 · Cited by 159
“Sheppard and coworkers examined the structural diversity within the Als protein family (49).”
BackgroundYeast Cell Adhesion Molecules Have Functional Amyloid-Forming Sequences
Ramsook, C. B., Tan, C., Garcia, M. C., Fung, R., Soybelman, G., Henry, R., Litewka, A., O'Meally, S., Otoo, H., Khalaf, R. A., et al. (2009) · Eukaryotic Cell · doi:10.1128/ec.00068-09 · Cited by 156
“Cells expressing ScFlo1p were slightly more birefringent than W303-1B (Fig.”
BackgroundInfluentialSpellberg, B. J., Ibrahim, A. S., Yeaman, M. R., Lin, L., Fu, Y., Avanesian, V., Bayer, A. S., Filler, S. G., Lipke, P. N., Otoo, H. N., et al. (2008) · Infection and Immunity · doi:10.1128/iai.00700-08 · Cited by 147
“aureus clumping factor, and related MSCRAMM proteins (26) influenced us to test the possibility of cross-kingdom protection against C.”
BackgroundMethodInfluentialSelf-citationAspergillus fumigatusMedA governs adherence, host cell interactions and virulence
Gravelat, F. N., Ejzykowicz, D. E., Chiang, L. Y., Chabot, J. C., Urb, M., MacDonald, K., Al-Bader, N., Filler, S. G., & Sheppard, D. C. (2009) · Cellular Microbiology · doi:10.1111/j.1462-5822.2009.01408.x · Cited by 138
“Adherence assays The capacity of the various strains of A. fumigatus to adhere to epithelial cells, plastic and endothelial cells was analysed using a modification of our previously described method (Sheppard et al., 2004a).”
MethodSelf-citationGlycan microarray analysis of Candida glabrata adhesin ligand specificity
Zupancic, M. L., Frieman, M., Smith, D., Alvarez, R. A., Cummings, R. D., & Cormack, B. P. (2008) · Molecular Microbiology · doi:10.1111/j.1365-2958.2008.06184.x · Cited by 143
“…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).”
BackgroundInfluentialCandida albicans Als Adhesins Have Conserved Amyloid-Forming Sequences
Otoo, H., Lee, K., Qiu, W.-G., & Lipke, P. (2007) · Eukaryotic Cell · doi:10.1128/ec.00309-07 · Cited by 139
“The Ig-like domains mediate adherence, and the TR increase the affinity of the Ig-like region for ligands and can also aggregate yeasts independently of the Ig-like region (12, 20, 24, 25, 29).”
BackgroundWhy doesCandida albicans switch?
Soll, D. R. (2009) · FEMS Yeast Research · doi:10.1111/j.1567-1364.2009.00562.x · Cited by 136
Tati, S., Davidow, P., McCall, A. D., Hwang-Wong, E., Rojas, I. G., Cormack, B. P., & Edgerton, M. (2016) · PLoS Pathogens · doi:10.1371/journal.ppat.1005522 · Cited by 146
“S150-2B pALS1 leu2 his3 trp1 ura3+pALS1 [55] C.”
InfluentialAdherence mechanisms in human pathogenic fungi
Tronchin, G., Pihet, M., Lopes-Bezerra, L. M., & Bouchara, J. (2008) · Medical Mycology · doi:10.1080/13693780802206435 · Cited by 139
A Role for Amyloid in Cell Aggregation and Biofilm Formation
Garcia, M. C., Lee, J. T., Ramsook, C. B., Alsteens, D., Dufrêne, Y. F., & Lipke, P. N. (2011) · PLoS ONE · doi:10.1371/journal.pone.0017632 · Cited by 128
“Nevertheless, expression in Saccharomyces cerevisiae has shown that Als1p, Als3p and Als5p bind similarly to a variety of substrates and are involved in endothelial cell adhesion, fungal aggregation, and tissue invasion [7,16,17,18,19].”
BackgroundCandida albicans Als proteins mediate aggregation with bacteria and yeasts.
Klotz, S., Gaur, N., Armond, R. L. D., Sheppard, D., Khardori, N., Edwards, J., Lipke, P., & El-azizi, M. (2007) · Medical Mycology · doi:10.1080/13693780701299333 · Cited by 125
Self-citationMurciano, C., Moyes, D. L., Runglall, M., Tobouti, P. L., Islam, A., Hoyer, L. L., & Naglik, J. R. (2012) · PLoS ONE · doi:10.1371/journal.pone.0033362 · Cited by 132
“Previously, a potential role for Als1 and Als5 in epithelial adhesion was suggested [35], which seems inconsistent with our results that demonstrate lack of an adhesive change in C.”
ResultPortrait of Candida Species Biofilm Regulatory Network Genes
Araújo, D., Henriques, M., & Silva, S. M. (2016) · Trends in Microbiology · doi:10.1016/j.tim.2016.09.004 · Cited by 140
Threonine-Rich Repeats Increase Fibronectin Binding in the Candidaalbicans Adhesin Als5p
Rauceo, J. M., De Armond, R., Otoo, H., Kahn, P. C., Klotz, S. A., Gaur, N. K., & Lipke, P. N. (2006) · Eukaryotic Cell · doi:10.1128/ec.00120-06 · Cited by 115
“CD spectroscopy studies have reported that Als5p(1-329) (Ig regions) and Als1p(1-432) (Ig-T regions) fragments have far UV CD spectra with a single minimum close to 212 nm, near the characteristic negative peak for proteins with mostly antiparallel -sheet and very little -helical content (17, 32).”
BackgroundResultInfluentialN-cadherin Mediates Endocytosis of Candida albicans by Endothelial Cells
Phan, Q. T., Fratti, R. A., Prasadarao, N. V., Edwards, J. E., & Filler, S. G. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m412592200 · Cited by 113
Self-citationNobbs, A. H., Vickerman, M. M., & Jenkinson, H. F. (2010) · Eukaryotic Cell · doi:10.1128/ec.00103-10 · Cited by 112
“There is some evidence that Als3p may promote attachment to fibronectin (39).”
BackgroundA study of the Candida albicans cell wall proteome
Castillo, L., Calvo, E., Martinez, A. I., Ruiz-Herrera, J., Valentín, E., López, J., & Sentandreu, R. (2008) · Proteomics · doi:10.1002/pmic.200800110 · Cited by 107
“They are probably involved in epithelial adhesion and invasiveness [14].”
BackgroundStrengthening relationships: amyloids create adhesion nanodomains in yeasts
Lipke, P. N., Garcia, M. C., Alsteens, D., Ramsook, C. B., Klotz, S. A., & Dufrêne, Y. F. (2012) · Trends in Microbiology · doi:10.1016/j.tim.2011.10.002 · Cited by 104
“In the initial unactivated state, Als proteins would bind to each other through rapidly dissociable hydrophobic effect interactions of the TR domains, and probably ligand binding of Ig domains [22, 25, 28, 55].”
BackgroundProteolytic Cleavage of Covalently Linked Cell Wall Proteins by Candida albicans Sap9 and Sap10
Schild, L., Heyken, A., de Groot, P. W. J., Hiller, E., Mock, M., de Koster, C., Horn, U., Rupp, S., & Hube, B. (2011) · Eukaryotic Cell · doi:10.1128/ec.00210-10 · Cited by 104
“Identified proteins belonged to the class of covalently linked GPI-modified cell wall proteins (GPI-CWPs), with functions from cell wall remodeling (Cht2, Ecm33, Pga4 and Rhd3) (14, 37, 39, 56) to host cell interaction and virulence (Ywp1, Als2, Ecm33, and Rhd3) (14, 24, 37, 64) and iron metabolism (Rbt5) (69) (Table…”
BackgroundInfluentialPathophysiological aspects of Aspergillus colonization in disease
Gago, S., Denning, D. W., & Bowyer, P. (2018) · Medical Mycology · doi:10.1093/mmy/myy076 · Cited by 122
“86 Recently, the importance of a putative GPI-anchored protein, cspA, in mediating A. fumigatus binding to the host has been evaluated in an in vitro model of infection using A549 alveolar epithelial cells.”
BackgroundCandida–host cell receptor–ligand interactions
Filler, S. G. (2006) · Current Opinion in Microbiology · doi:10.1016/j.mib.2006.06.005 · Cited by 100
Self-citationCandida albicans Interactions with Mucosal Surfaces during Health and Disease
Nikou, S.-A., Kichik, N., Brown, R., Ponde, N., Ho, J., Naglik, J., & Richardson, J. (2019) · Pathogens · doi:10.3390/pathogens8020053 · Cited by 103
Biofilm Exopolysaccharides of Pathogenic Fungi: Lessons from Bacteria
Sheppard, D. C., & Howell, P. L. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.r116.720995 · Cited by 129
Self-citationMolecular Mechanism of Aspergillus fumigatus Adherence to Host Constituents
Sheppard, D. (2011) · Current Opinion in Microbiology · doi:10.1016/j.mib.2011.07.006 · Cited by 102
“In this organism, glycosylphosphatidylinositol (GPI) anchored, serine-threonine rich proteins containing internal tandem repeats have been described as key effectors of fungal adherence [14,15].”
Self-citationAdvancements and challenges in antifungal therapeutic development
Puumala, E., Fallah, S., Robbins, N., & Cowen, L. E. (2024) · Clinical Microbiology Reviews · doi:10.1128/cmr.00142-23 · Cited by 128
“…an immunodominant C. albicans cell wall protein that is characterized by three domains: an N-terminal region, which is conserved among Als proteins; a central portion containing variable tandem repeats; and a serine-rich C-terminal region containing a glycosylphosphatidylinositol anchor (131, 132).”
BackgroundGenetic and epigenetic mechanisms underlying cell-surface variability in protozoa and fungi.
Verstrepen, K., & Fink, G. (2009) · Annual Review of Genetics · doi:10.1146/annurev-genet-102108-134156 · Cited by 97
Sztukowska, M. N., Dutton, L. C., Delaney, C., Ramsdale, M., Ramage, G., Jenkinson, H. F., Nobbs, A. H., & Lamont, R. J. (2018) · mBio · doi:10.1128/mbio.00202-18 · Cited by 96
NDV-3 protects mice from vulvovaginal candidiasis through T- and B-cell immune response
Ibrahim, A. S., Luo, G., Gebremariam, T., Lee, H.-K., Schmidt, C. S., Hennessey, J. P., French, S. W., Yeaman, M. R., Filler, S. G., & Edwards, J. E. (2013) · Vaccine · doi:10.1016/j.vaccine.2013.09.016 · Cited by 102
“albicans cell surface agglutinin-like sequence 3 protein (Als3p), plays a key role in multiple processes that are necessary for disease initiation and progression including adherence to host cells [10, 11], biofilm formation [11, 12], host cell invasion [13], and iron acquisition [14].”
BackgroundSelf-citationCandida albicans CUG Mistranslation Is a Mechanism To Create Cell Surface Variation
Miranda, I. M., Silva-Dias, A., Rocha, R., Teixeira‐Santos, R., Coelho, C., Gonçalves, T., Santos, M. A. S., Pina‐Vaz, C., Solis, N. V., Filler, S. G., et al. (2013) · mBio · doi:10.1128/mbio.00285-13 · Cited by 94
“albicans ALS3-Leu and ALS3-Ser genes (20).”
BackgroundMethodInfluentialSelf-citationLi, F., & Palecek, S. P. (2008) · Microbiology · doi:10.1099/mic.0.2007/013789-0 · Cited by 91
“Adherence activity of the GPI-anchored proteins has commonly been ascribed to the N-terminal domains of these proteins because deletions in these regions usually abrogate binding activity (Frieman et al., 2002; Loza et al., 2004; Sheppard et al., 2004; Staab & Sundstrom, 1998; Wojciechowicz et al., 1993).”
BackgroundGenomewide Expression Profile Analysis of the Candida glabrata Pdr1 Regulon
Caudle, K. E., Barker, K. S., Wiederhold, N. P., Xu, L., Homayouni, R., & Rogers, P. D. (2010) · Eukaryotic Cell · doi:10.1128/ec.00073-10 · Cited by 92
“albicans have been shown to confer distinct adhesion profiles toward human proteins and cells (29).”
BackgroundMechanisms of Candida albicans Trafficking to the Brain
Liu, Y., Mittal, R., Solis, N. V., Prasadarao, N. V., & Filler, S. G. (2011) · PLoS Pathogens · doi:10.1371/journal.ppat.1002305 · Cited by 93
“albicans to HUVECs and HBMECs grown in 6-well tissue culture plates was measured by a modification of our previously described method [25].”
BackgroundMethodInfluentialSelf-citationAdhesins of Yeasts: Protein Structure and Interactions
Willaert, R. (2018) · Journal of Fungi · doi:10.3390/jof4040119 · Cited by 109
Salgado, P. S., Yan, R., Taylor, J. D., Burchell, L., Jones, R., Hoyer, L. L., Matthews, S., Simpson, P. J., & Cota, E. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1103496108 · Cited by 85
“Despite the ability to recognize a range of unrelated substrates, there are documented differences in ligand specificity between Als proteins (10, 11), potentially due to variations in C-terminal peptide sequences that can be accommodated in the binding clefts of their respective N-terminal adhesins.”
BackgroundThe multitude of targets for the immune system and drug therapy in the fungal cell wall.
Nimrichter, L., Rodrigues, M., Rodrigues, E., & Travassos, L. (2005) · Microbes and infection · doi:10.1016/j.micinf.2005.03.002 · Cited by 91
Protein Glycosylation in Candida
Mora-Montes, H. M., Ponce‐Noyola, P., Villagómez-Castro, J. C., Gow, N. A. R., Flores-Carreón, A., & López-Romero, E. (2009) · Future Microbiology · doi:10.2217/fmb.09.88 · Cited by 92
Aspergillus fumigatus CalA binds to integrin α5β1 and mediates host cell invasion
Liu, H., Lee, M. J., Solis, N. V., Phan, Q. T., Swidergall, M., Ralph, B., Ibrahim, A. S., Sheppard, D. C., & Filler, S. G. (2016) · Nature Microbiology · doi:10.1038/nmicrobiol.2016.211 · Cited by 97
Self-citationGrubb, S. E. W., Murdoch, C., Sudbery, P. E., Saville, S. P., Lopez-Ribot, J. L., & Thornhill, M. H. (2008) · Infection and Immunity · doi:10.1128/iai.00332-08 · Cited by 87
“These include proteins with integrin-like properties (reviewed in references 32 and 36), Candida agglutinin-like sequence (ALS) gene products (72, 84), and mannans (57).”
BackgroundLinder, T., & Gustafsson, C. M. (2007) · Fungal Genetics and Biology · doi:10.1016/j.fgb.2007.08.002 · Cited by 80
Modular determinants of antimicrobial activity in platelet factor-4 family kinocidins.
Yeaman, M., Yount, N., Waring, A., Gank, K. D., Kupferwasser, D., Wiese, R., Bayer, A., & Welch, W. (2007) · Biochimica et Biophysica Acta · doi:10.1016/j.bbamem.2006.11.010 · Cited by 86
“Secondary structures of cPMP library peptides were assessed by circular dichroism (CD) as previously detailed [22].”
MethodSelf-citationRomo, J. A., & Kumamoto, C. A. (2020) · Journal of Fungi · doi:10.3390/jof6010016 · Cited by 106
Ibrahim, A. S., Spellberg, B. J., Avenissian, V., Fu, Y., Filler, S. G., & Edwards, J. E. (2005) · Infection and Immunity · doi:10.1128/iai.73.2.999-1005.2005 · Cited by 83
“albicans adherence to endothelial cells (32), and because of its potential immunological cross-reactivity with other members of the Als family of proteins (54).”
BackgroundSelf-citationIbrahim, A., Spellberg, B., Avanesian, V., Fu, Y., & Edwards, J. (2006) · Infection and Immunity · doi:10.1128/iai.74.5.3039-3041.2006 · Cited by 83
“A high degree of purity (90%) was confirmed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis as well as circular dichroism and Fourier transform infrared microscopy, as described previously ( 10 ).”
BackgroundSelf-citationFungal Cell Wall Proteins and Signaling Pathways Form a Cytoprotective Network to Combat Stresses
Ibe, C., & Munro, C. A. (2021) · Journal of Fungi · doi:10.3390/jof7090739 · Cited by 88
What We Do Not Know about Fungal Cell Adhesion Molecules
Lipke, P. N. (2018) · Journal of Fungi · doi:10.3390/jof4020059 · Cited by 99
Lin, J., Oh, S.-H., Jones, R., Garnett, J. A., Salgado, P. S., Rusnakova, S., Matthews, S., Hoyer, L. L., & Cota, E. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.547877 · Cited by 91
“Initial speculation about the Als ligand-binding mechanism suggested that it occurs by interactions between the NT-Als surface and the surface of the ligand (8, 16, 32).”
BackgroundMartínez-López, R., Park, H., Myers, C., Gil, C., & Filler, S. (2006) · Eukaryotic Cell · doi:10.1128/ec.5.1.140-147.2006 · Cited by 81
“albicans hyphae, where it functions as an adhesin (10, 11, 27).”
BackgroundSelf-citationFungal invasion of epithelial cells
Yang, W., Yan, L., Wu, C., Zhao, X., & Tang, J. (2014) · Microbiological Research · doi:10.1016/j.micres.2014.02.013 · Cited by 79
“2004; Sheppard et al. 2004; Rauceo et al. 2006), the Nerminal domain is composed of a signal peptide followed by an mmunoglobulin-like domain and a threonine-rich domain conaining anti-parallel -sheets (Hoyer and Hecht 2001; Sheppard t al.”
BackgroundInfluentialInnate immune cell response uponCandida albicansinfection
Qin, Y., Zhang, L., Xu, Z. Q., Zhang, J., Jiang, Y., Cao, Y., & Yan, T. (2016) · Virulence · doi:10.1080/21505594.2016.1138201 · Cited by 83
Alves, C. T., Wei, X., Silva, S. M., Azeredo, J., Henriques, M., & Williams, D. W. (2014) · Journal of Infection · doi:10.1016/j.jinf.2014.06.002 · Cited by 84
Gene Overexpression/Suppression Analysis of Candidate Virulence Factors of Candida albicans
Fu, Y., Luo, G., Spellberg, B. J., Edwards, J. E., & Ibrahim, A. S. (2008) · Eukaryotic Cell · doi:10.1128/ec.00445-07 · Cited by 70
“albicans include proteins that mediate adherence to and invasion of host tissues (43), morphological change from yeast to hyphae (29, 30), secretion of lytic enzymes (17, 27, 41), maintenance of cell wall integrity (55), and avoidance of the host immune response (39).”
BackgroundSelf-citationStructural congruence among membrane-active host defense polypeptides of diverse phylogeny.
Yount, N., & Yeaman, M. (2006) · Biochimica et Biophysica Acta · doi:10.1016/j.bbamem.2006.03.027 · Cited by 72
Self-citationFernández-Álvarez, A., Elías-Villalobos, A., & Ibeas, J. (2009) · The Plant Cell Online · doi:10.1105/tpc.109.065839 · Cited by 71
“Cell wall glycoproteins have been identified as fungal adhesives and have been implicated in host cell adhesion in many organisms (Gaur and Klotz, 1997; Buck and Andrews, 1999; Frieman et al., 2002; Sheppard et al., 2004).”
BackgroundRas Signaling Gets Fine-Tuned: Regulation of Multiple Pathogenic Traits of Candida albicans
Inglis, D. O., & Sherlock, G. (2013) · Eukaryotic Cell · doi:10.1128/ec.00094-13 · Cited by 67
“This family, and Als3 in particular, is involved in cell adhesion and mediates attachment to endothelial cells (63), epithelial cells, and extracellular matrix proteins (64).”
BackgroundHan, G., Liu, N., Li, C., Tu, J., Li, Z., & Sheng, C. (2020) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.0c00102 · Cited by 85
Green, C. B., Zhao, X., Yeater, K. M., & Hoyer, L. L. (2005) · Microbiology · doi:10.1099/mic.0.27696-0 · Cited by 64
“One example is the ALS (agglutinin-like sequence) gene family that encodes cell-surface glycoproteins involved in adhesion to host surfaces and potentially other cellular processes (Gaur & Klotz, 1997; Hoyer, 2001; Fu et al., 2002; Zhao et al., 2004; Sheppard et al., 2004).”
Background
Metadata
- Authors
- Sheppard, D. C., Yeaman, M. R., Welch, W. H., Phan, Q. T., Fu, Y., Ibrahim, A. S., Filler, S. G., Zhang, M., Waring, A. J., & Edwards, J. E.
- Affiliations
- University of California, Los Angeles (US)
- University of Nevada, Reno (US)
- California State University, Long Beach (US)
- Corresponding author
- Sheppard, Donald C.
- ORCID
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2004-07
- Volume
- 279
- Issue
- 29
- Pages
- 30480-30489
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1968095975
- Cited by
- 300
- References
- 59
- Citations by year
- 2026: 9 · 2025: 7 · 2024: 5 · 2023: 9 · 2022: 10 · 2021: 15 · 2020: 15 · 2019: 7 · 2018: 14 · 2017: 11 · 2016: 11 · 2015: 12 · 2014: 27 · 2013: 16 · 2012: 13
- FWCI
- 6.17
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases (P01 AI-37194, R01AI019990, R01 AI-48031, R03AI054531, R01-AI19990, R01AI054928, R01AI048031, P01AI037194)
- National Institute of Dental and Craniofacial Research (R01DE013974, 5R01 DE13974)
- National Center for Research Resources (M01RR000425, M01-RR00425)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Health Sciences › Medicine › Infectious Diseases › Fungal Infections and Studies
- Keywords
- Candida albicans, fungal adhesion, endothelial cell invasion, N-terminal domain, antiparallel beta-sheet, cell wall proteins, host-pathogen interaction, fusion protein
- MeSH terms
- Amino Acid Sequence, Candida albicans, Cell Adhesion, Cell Wall, Circular Dichroism, Cloning, Molecular, Endothelium, Vascular, Epithelial Cells, Flow Cytometry, Fungal Proteins, Multigene Family, Humans, Membrane Glycoproteins, Models, Molecular, Molecular Sequence Data, Plasmids, Recombinant Fusion Proteins, Saccharomyces cerevisiae, Substrate Specificity, Cell Adhesion Molecules, Polymerase Chain Reaction, Protein Structure, Secondary, Protein Structure, Tertiary, Spectroscopy, Fourier Transform Infrared, DNA Primers, Amino Acid Motifs, Cell Line, Tumor
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