<i>Candida albicans</i>Als proteins mediate aggregation with bacteria and yeasts

Klotz, Stephen A.; Gaur, Nand K.; Armond, Richard De; Sheppard, Donald C.; Khardori, N.M.; Edwards, John E.; Lipke, Peter N.; El-Azizi, Mohamed

doi:10.1080/13693780701299333

Cited by 108 publications

(92 citation statements)

References 27 publications

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“…Among them, mannans could be one of the potential surface ligands because these polysaccharides are particularly abundant at the outermost layer (Gow et al 2012). However, the composition and molecular architecture of the cell wall of C. albicans are quite complex (Klotz et al 2007;Li and Palecek 2008), and other surface-associated glycoproteins and adhesins (e.g., Als and Eap1) potentially interact with GtfB. Clearly, further studies are needed to identify the binding partners as well as their spatial localization on the fungal surface that mediates GtfB-C. albicans adhesion.…”

Section: Discussionmentioning

confidence: 99%

Binding Force Dynamics of Streptococcus mutans–glucosyltransferase B to Candida albicans

et al. 2015

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Candida albicans cells are often detected with Streptococcus mutans in plaque biofilms from children affected with early childhood caries. The coadhesion between these 2 organisms appears to be largely mediated by the S. mutans-derived exoenzyme glucosyltransferase B (GtfB); GtfB readily binds to C. albicans cells in an active form, producing glucans locally that provide enhanced binding sites for S. mutans. However, knowledge is limited about the mechanisms by which the bacterial exoenzyme binds to and functions on the fungal surface to promote this unique cross-kingdom interaction. In this study, we use atomic force microscopy to understand the strength and binding dynamics modulating GtfB-C. albicans adhesive interactions in situ. Single-molecule force spectroscopy with GtfB-functionalized atomic force microscopy tips demonstrated that the enzyme binds with remarkable strength to the C. albicans cell surface (~2 nN) and showed a low dissociation rate, suggesting a highly stable bond. Strikingly, the binding strength of GtfB to the C. albicans surface was ~2.5-fold higher and the binding stability, ~20 times higher, as compared with the enzyme adhesion to S. mutans. Furthermore, adhesion force maps showed an intriguing pattern of GtfB binding. GtfB adhered heterogeneously on the surface of C. albicans, showing a higher frequency of adhesion failure but large sections of remarkably strong binding forces, suggesting the presence of GtfB binding domains unevenly distributed on the fungal surface. In contrast, GtfB bound uniformly across the S. mutans cell surface with less adhesion failure and a narrower range of binding forces (vs. the C. albicans surface). The data provide the first insights into the mechanisms underlying the adhesive and mechanical properties governing GtfB interactions with C. albicans. The strong and highly stable GtfB binding to C. albicans could explain, at least in part, why this bacterially derived exoenzyme effectively modulates this virulent cross-kingdom interaction.

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Section: Discussionmentioning

confidence: 99%

Binding Force Dynamics of Streptococcus mutans–glucosyltransferase B to Candida albicans

et al. 2015

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“…S. gordonii also binds to C. albicans Als5 (27). Other Grampositive cocci, including Staphylococcus aureus, Staphylococcus epidermidis, and Streptococcus pyogenes, also adhere to C. albicans (44).…”

Section: Als3 Functionmentioning

confidence: 99%

Candida albicans Als3, a Multifunctional Adhesin and Invasin

2011

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2Candida albicans is part of the normal human flora, and it grows on mucosal surfaces in healthy individuals. In susceptible hosts, this organism can cause both mucosal and hematogenously disseminated disease. For C. albicans to persist in the host and induce disease, it must be able to adhere to biotic and abiotic surfaces, invade host cells, and obtain iron. The C. albicans hypha-specific surface protein Als3 is a member of the agglutininlike sequence (Als) family of proteins and is important in all of these processes. Functioning as an adhesin, Als3 mediates attachment to epithelial cells, endothelial cells, and extracellular matrix proteins. It also plays an important role in biofilm formation on prosthetic surfaces, both alone and in mixed infection with Streptococcus gordonii. Als3 is one of two known C. albicans invasins. It binds to host cell receptors such as E-cadherin and N-cadherin and thereby induces host cells to endocytose the organism. Als3 also binds to host cell ferritin and enables C. albicans to utilize this protein as a source of iron. Because of its multiple functions and its high expression level in vivo, Als3 is a promising target for vaccines that induce protective cell-mediated and antibody responses. This review will summarize the multiple functions of this interesting and multifunctional protein.Candida spp. are the fourth most common cause of nosocomial bloodstream infections, and Candida albicans accounts for approximately 50% of cases of candidemia (20,67). This organism also causes at least 80% of cases of oropharyngeal and vulvovaginal candidiasis (57, 66). The predominance of C. albicans as a cause of both hematogenously disseminated and mucosal disease suggests that this organism possesses unique virulence factors compared to other species of Candida. One such factor, which is present only in C. albicans, is Als3. This protein plays a key role in multiple processes that are necessary for the organism to colonize the host and cause disease. These processes include adherence to host cells, biofilm formation, host cell invasion, and iron acquisition. Moreover, because Als3 is highly expressed in vivo, it is a promising target for therapeutic antibody and vaccine development. This review will discuss Als3 structure and function, as well as its utility as a therapeutic target. GENETIC AND BIOCHEMICAL CHARACTERISTICS OF Als3The ALS gene family. Als3 is encoded by the ALS3 gene, which is a member of the agglutinin-like sequence (ALS) gene family (23). This family was discovered by Hoyer et al. (24) based on its similarity to Saccharomyces cerevisiae SAG1, which codes for ␣ agglutinin. The ALS gene family has eight members (ALS1 to ALS7 and ALS9) (Fig. 1). These genes encode cell surface proteins that are predicted to share the same overall structure (Fig. 2). At the N terminus is a signal peptide followed by a 300-amino-acid immunoglobulin-like domain and a 104-amino-acid threonine-rich domain that contains ␤-sheets (18,22,47,55). Most Als proteins have adhesin function (18,55,72), an...

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“…118,119 An in vitro model of various C. albicans-bacterial biofilms concluded that bacteria negatively impact C. albicans biofilm formation by inhibiting fungal growth and suppressing genes responsible for hyphae formation. 120 Peleg et al 121 described 5 types of bacterial-fungal interactions and many speculate these also take place within the vagina: physical interactions, 122,123 chemical exchanges, 124 use of metabolic byproducts, 109,118 changes in the environment, 124 and alteration of the host immune response. 125 Further studies are required to better understand this important relationship between vaginal bacteria, Candida spp.…”

Section: 100mentioning

confidence: 99%

“…Interactions between Candida and microbiota at the mucosal interface have profound effects on the vaginal ecosystem. 109,[120][121][122][123][124][125] Metabolites and small molecules made by the microbiota affect the metabolism and morphology of Candida species. Changes in microbiota relative abundance also impact the abundance of Candida and its ability to access the mucosal surface, where invasion occurs.…”

Section: Importance Of the Fungal Mycobiomementioning

confidence: 99%

The vaginal mycobiome: A contemporary perspective on fungi in women's health and diseases

2016

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Most of what is known about fungi in the human vagina has come from culture-based studies and phenotypic characterization of single organisms. Though valuable, these approaches have masked the complexity of fungal communities within the vagina. The vaginal mycobiome has become an emerging field of study as genomics tools are increasingly employed and we begin to appreciate the role these fungal communities play in human health and disease. Though vastly outnumbered by its bacterial counterparts, fungi are important constituents of the vaginal ecosystem in many healthy women. Candida albicans, an opportunistic fungal pathogen, colonizes 20% of women without causing any overt symptoms, yet it is one of the leading causes of infectious vaginitis. Understanding its mechanisms of commensalism and pathogenesis are both essential to developing more effective therapies. Describing the interactions between Candida, bacteria (such as Lactobacillus spp.) and other fungi in the vagina is fundamental to our characterization of the vaginal mycobiome.

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Candida albicansAls proteins mediate aggregation with bacteria and yeasts

Cited by 108 publications

References 27 publications

Binding Force Dynamics of Streptococcus mutans–glucosyltransferase B to Candida albicans

Binding Force Dynamics of Streptococcus mutans–glucosyltransferase B to Candida albicans

Candida albicans Als3, a Multifunctional Adhesin and Invasin

The vaginal mycobiome: A contemporary perspective on fungi in women's health and diseases

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