Plasma and extracellular matrix proteins mediate in the fate of Candida albicans in the human host (original) (raw)
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Interaction of human fibronectin with Candida glabrata epithelial adhesin 6 (Epa6)
Acta Biochimica Polonica, 2016
Adherence of pathogens to extracellular matrix proteins and host cells is one of the essential steps in the microbial colonization of the human organism. The adhesion of C. glabrata, i.e. the second major causative agent of human disseminated candidiases after C. albicans, to the host epithelium mainly engages specific fungal cell wall proteins—epithelial adhesins (Epa)—in particular, Epa1, Epa6 and Epa7. The aim of the present study was to identify the major Epa protein involved in the interactions with the human extracellular matrix protein—fibronectin—and to present the kinetic and thermodynamic characteristics of these interactions. A relatively novel gel-free approach, i.e. the “cell surface shaving” that consists in short treatment of fungal cells with trypsin was employed to identify the C. glabrata surfaceome. Epa6 was purified, and the isolated protein was characterized in terms of its affinity to human fibronectin using a microplate ligand-binding assay and surface plasmo...
Journal of Biological Chemistry, 1998
Host infection by the pathogenic fungus Candida albicans is initiated by adhesion and mediated by binding to several host extracellular matrix proteins. Previously, we demonstrated that hemoglobin supplemented into a chemically defined medium significantly and specifically induced fibronectin binding to C. albicans. We now report that hemoglobin also induces binding of laminin, fibrinogen, and type IV collagen but not of thrombospondin-1 or type I collagen. The binding of each protein was inhibited by the respective unlabeled ligand in a concentration-dependent manner. Fibrinogen inhibited the binding of radiolabeled fibronectin, laminin, and fibrinogen with similar IC 50 values, suggesting that a single promiscuous receptor recognizes these three proteins. Competitive binding studies indicated that a second class of receptor binds specifically to laminin. Growth of C. albicans in the presence of hemoglobin also increased cell adhesion to immobilized fibronectin, laminin, fibrinogen, and type IV collagen but not to thrombospondin-1 or type I collagen. Exposure to hemoglobin induced increased or de novo expression of several surface proteins on C. albicans. One of these proteins with a molecular weight of 55,000 recognized fibronectin, based on ligand protection and affinity chromatography on immobilized fibronectin. Thus, hemoglobin induces both promiscuous and specific receptors for extracellular matrix proteins and, therefore, may regulate matrix adhesion during dissemination of C. albicans infections. Candida albicans is an important opportunistic pathogen for humans, causing both superficial and disseminated infections (reviewed in Refs. 1 and 2) with significant morbidity and mortality among immunocompromised patients (3). Adhesion of the organism to mucosal epithelium is a prerequisite for colonization and, therefore, is regarded as an initial step in the process leading to infections (3, 4). Additional adhesion events to endothelium and extracellular matrix (ECM) 1 components are required for dissemination of C. albicans.
The Recognition of Host Cells by the Pathogenic Yeast, Candida albicans
Nippon Ishinkin Gakkai Zasshi, 1994
Candida albicans is a pathogen of mucosal surfaces but can also cause systemic disease. Its evolution into a commensal and frequent pathogen of humans and animals progressed as the organism developed specific traits which allowed it to survive in a host. One can only speculate as to which traits promoted its survival; however, it would seem that recognition and colonization of host cells would afford a selective advantage over those organisms which could not adhere. Also, colonization could permit egress of the organism into tissues and, with that, escape from the competitive microbial ecology of mucosal surfaces. Recognition of host cells by C. albicans has been the focus of study by a number of investigators. Based upon a number of observations by several research groups, the recognition process appears complex and dependent upon the type of host cell studied. The C. albicans adhesins are cell surface macromolecules, one adhesin resembling the "integrin" receptors of mammalian cells. Based upon functional activity and the type of host cell molecule recognized by the organism, five adhesin systems have been described. Four of these adhesins are mannoprotein or mannan, while the fifth is thought to be chitin. The host cell ligand is either carbohydrate (fucosyl or glucosamine glycosides) or protein (arginine-glycine-aspartic acid, RGD peptide), depending upon the type of host cell, i. e., either epithelial or endothelial. The study of the Candida adhesins is now beginning to shift from its descriptive beginnings to molecular approaches with the ultimate intent of establishing the role of these molecules in virulence.
Candida albicans adhesins: Biochemical aspects and virulence
Revista iberoamericana de micología, 1997
The recognition of host cells by the pathogenic yeast, Candida albicans, is probably an essential step in the pathogenesis of disease development. The interaction of yeast and hyphal mannoproteins with host cell receptors has been studied by a number of laboratories. C. albicans recognizes a variety of host cells as well as host cell extracellular matrix proteins. This observation is not unexpected given the number of sites within and on the body which can be colonized and infected by the organism. Indeed, it would appear that C. albicans has evolved a number of ways in which it recognizes the host. This statement is made with the qualification that the organism uses other processes to infect, such as morphogenesis, phenotypic switching and the production of invasive enzymes, including secreted aspartyl proteases and phosholipases. Recognition of epithelial cells is accomplished through cell surface mannoproteins (adhesins) which bind to carbohydrate-containing receptors. The number...
BMC Microbiology, 2015
Background: Candida parapsilosis and C. tropicalis increasingly compete with C. albicans-the most common fungal pathogen in humans-as causative agents of severe candidiasis in immunocompromised patients. In contrast to C. albicans, the pathogenic mechanisms of these two non-albicans Candida species are poorly understood. Adhesion of Candida yeast to host cells and the extracellular matrix is critical for fungal invasion of hosts. Methods: The fungal proteins involved in interactions with extracellular matrix proteins were isolated from mixtures of β-1,3-glucanaseor β-1,6-glucanase-extractable cell wall-associated proteins by use of affinity chromatography and chemical cross-linking methods, and were further identified by liquid chromatography-coupled tandem mass spectrometry. Results: In the present study, we characterized the binding of three major extracellular matrix proteins-fibronectin, vitronectin and laminin-to C. parapsilosis and C. tropicalis pseudohyphae. The major individual compounds of the fungal cell wall that bound fibronectin, vitronectin and laminin were found to comprise two groups: (1) true cell wall components similar to C. albicans adhesins from the Als, Hwp and Iff/Hyr families; and (2) atypical (cytoplasmderived) surface-exposed proteins, including malate synthase, glucose-6-phosphate isomerase, 6-phosphogluconate dehydrogenase, enolase, fructose-1,6-bisphosphatase, transketolase, transaldolase and elongation factor 2. Discussion: The adhesive abilities of two investigated non-albicans Candida species toward extracellular matrix proteins were comparable to those of C. albicans suggesting an important role of this particular virulence attribute in the pathogenesis of infections caused by C. tropicalis and C. parapsilosis. Conclusions: Our results reveal new insight into host-pathogen interactions during infections by two important, recently emerging, fungal pathogens.
Adhesins in Human Fungal Pathogens: Glue with Plenty of Stick
Eukaryotic Cell, 2013
Understanding the pathogenesis of an infectious disease is critical for developing new methods to prevent infection and diagnose or cure disease. Adherence of microorganisms to host tissue is a prerequisite for tissue invasion and infection. Fungal cell wall adhesins involved in adherence to host tissue or abiotic medical devices are critical for colonization leading to invasion and damage of host tissue. Here, with a main focus on pathogenic Candida species, we summarize recent progress made in the field of adhesins in human fungal pathogens and underscore the importance of these proteins in establishment of fungal diseases.
Journal of Biological Chemistry, 1994
A 30-kDa proteolytic fragment from the gelatidcollagen-binding domain of fibronectin is a potent inhibitor of fibronectin binding to Candida albicans, with a molar inhibition constant equal to that of intact fibronectin. Recombinant and proteolytic fragments from the cell-, the fibrin I-, and the heparin II-binding domains also inhibit fibronectin binding, but are 13-1000-fold less active. In suspension, binding of fibronectin to C. albicans is regulated by growth conditions and is specific, saturable, time-dependent, reversible, and divalent cationindependent. Scatchard plot analyses indicate the presence of high affinity (K, = 1.3 x lo-' M) and low affinity (K, = 1.2 x lo-' M) receptors. Recombinant or proteolytic fragments from four binding domains of fibronectin promote adhesion of C. albicans. A recombinant fragment corresponding to the cell-binding domain but with the sequence Arg-Gly-Asp-Ser deleted promotes C. albicans adhesion and inhibits fibronectin binding to C. albicans with the same activity as the natural sequence. Furthermore, four peptides containing the Arg-Gly-Asp sequence and the peptides CS-1 and Arg-Glu-Asp-Val did not block the binding of fibronectin to C. albicans. Thus, in contrast to the specific binding of soluble fibronectin, recognition of immobilized fibronectin by C. albicans is mediated by several domains of the protein. Interactions with the cell-binding domain are not mediated by the Arg-Gly-Asp or other known recognition sequences as it has been suggested. Binding of fibronectin also did not correlate with C,d binding to the avirulent clones of C. albicans strain HI, or with iC,b binding to variants of the strain 4918. Candida albicans is a human pathogen that causes hematogenous infection with increasing frequency in neonates, immunocompromised patients, and in the hyperglycemic or hyperalimented host (1-3). The gravest complication of the disease is the establishment of disseminated infections, resulting in such clinical entities as endocarditis, nephritis,and endophthalmitis. Attachment of C. albicans to the host extracellular matrix or to endothelial and epithelial cells is a critical step in the initiation of infection (4). Knowledge of the mechanism for attachment of C. albicans to the extracellular matrix or host cells could lead to development of a novel class of antifungal agents whose mechanism of action would be to compete with the endogenous ligands for binding to the pathogen receppayment of page charges. This article must therefore be hereby marked * The costs of publication of this article were defrayed in part by the "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Adherence of Candida albicans to host cells
FEMS Microbiology Letters, 1995
Research devoted to uncovering the mechanisms of adherence of Candida albicans to human tissue is reviewed. The physical aspects of adherence of the fungus to host cells and the biochemical and molecular features, as far as they are known, are discussed. Relevant pre-and post-adherence events in the pathogenesis of disease caused by this fungus are also noted. Putative adhesins and surface receptors of C. albicans for host proteins are discussed in detail.