Candida albicans Uses the Surface Protein Gpm1 to Attach to Human Endothelial Cells and to Keratinocytes via the Adhesive Protein Vitronectin

Lopez, Crisanto M.; Wallich, Reinhard; Riesbeck, Kristian; Skerka, Christine; Zipfel, Peter F.

doi:10.1371/journal.pone.0090796

Cited by 57 publications

(54 citation statements)

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“…capri (47). Pgm and Pyk were confirmed in different bacterial species and in Candida albicans as surface localized and partly involved in interactions with host factors (48)(49)(50)(51)(52). To our knowledge, the surface localization of Ldh has been reported for the first time.…”

Section: Discussionmentioning

confidence: 62%

“…In addition to PdhA, PdhB, and GapA, other glycolytic enzymes such as lactate dehydrogenase (Ldh) are detected in the Triton X-100-insoluble fraction that represents the membrane-associated proteins of M. pneumoniae (28). Finally, additional glycolytic enzymes are described in other bacterial species but have not hitherto been characterized in mycoplasmas as surface displayed, indicating a role for other proteins as potential interaction partners with host factors (29)(30)(31)(32). In summary, the present information regarding surface-localized glycolytic enzymes suggests a complex network of interactions with different host factors, which may be important in understanding the pathogenesis of M. pneumoniae infections.…”

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confidence: 99%

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Network of Surface-Displayed Glycolytic Enzymes in Mycoplasma pneumoniae and Their Interactions with Human Plasminogen

et al. 2016

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In different bacteria, primarily cytosolic and metabolic proteins are characterized as surface localized and interacting with different host factors. These moonlighting proteins include glycolytic enzymes, and it has been hypothesized that they influence the virulence of pathogenic species. The presence of surface-displayed glycolytic enzymes and their interaction with human plasminogen as an important host factor were investigated in the genome-reduced and cell wall-less microorganism Mycoplasma pneumoniae, a common agent of respiratory tract infections of humans. After successful expression of 19 glycolytic enzymes and production of polyclonal antisera, the localization of proteins in the mycoplasma cell was characterized using fractionation of total proteins, colony blot, mild proteolysis and immunofluorescence of M. pneumoniae cells. Eight glycolytic enzymes, pyruvate dehydrogenases A to C (PdhA-C), glyceraldehyde-3-phosphate dehydrogenase (GapA), lactate dehydrogenase (Ldh), phosphoglycerate mutase (Pgm), pyruvate kinase (Pyk), and transketolase (Tkt), were confirmed as surface expressed and all are able to interact with plasminogen. Plasminogen bound to recombinant proteins PdhB, GapA, and Pyk was converted to plasmin in the presence of urokinase plasminogen activator and plasmin-specific substrate D-valyl-leucyl-lysine-p-nitroanilide dihydrochloride. Furthermore, human fibrinogen was degraded by the complex of plasminogen and recombinant protein PdhB or Pgm. In addition, surface-displayed proteins (except PdhC) bind to human lung epithelial cells, and the interaction was reduced significantly by preincubation of cells with antiplasminogen. Our results suggest that plasminogen binding and activation by different surface-localized glycolytic enzymes of M. pneumoniae may play a role in successful and long-term colonization of the human respiratory tract. Members of the class Mollicutes are known to be the smallest and simplest self-replicating prokaryotes. Among them, Mycoplasma pneumoniae is a common pathogen in humans. The cell wall-less bacterium causes infections of the respiratory tract, including severe interstitial pneumonia (1), and usually accounts for 5 to 10% of all cases of community-acquired pneumonia among pediatric (2) and adult (3) patients. Because of the timedependent incidence of infections, Ͼ25% of pneumonia cases in epidemic periods are attributed to this agent (4). In addition, a number of extrapulmonary manifestations and complications are described, affecting mainly the skin and the central nervous system (5).Due to the greatly reduced genome of M. pneumoniae (816 kbp, 689 open reading frames [ORFs]), the metabolic pathways and the repertoire of virulence factors are limited (6). However, M. pneumoniae has developed effective strategies to infect humans and allow long-term survival in the respiratory mucosa. These include the targeted adherence of the bacteria to epithelial cells via a specialized complex of adhesins and adhesion-related proteins (7) as the first step in colonization,...

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Section: Discussionmentioning

confidence: 62%

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confidence: 99%

Network of Surface-Displayed Glycolytic Enzymes in Mycoplasma pneumoniae and Their Interactions with Human Plasminogen

et al. 2016

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“…Previous studies have shown that Sod1 interacts with macrophages while Sod2 is required to resist neutrophil attack [19]. Sod4, Sod5 [20] and Sod6, along with the catalase Cta1 detoxify extracellular ROS produced by macrophages [21].…”

Section: Discussionmentioning

confidence: 99%

Flow Cytometry Assessment of Bacterial and Yeast Induced Oxidative Burst in Peripheral Blood Phagocytes

Șular

Dobreanu

2017

Acta Medica Marisiensis

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Objective: The aim of this study was to verify in our laboratory conditions the performance criteria of a commercial kit (Phagoburst TM , Glycotope Biotechnology) as described by the producers. We have also partially altered the use of the available kit by introducing a non-opsonized Candida albicans stimulus, in addition to the opsonized Escherichia coli stimulus provided by the manufacturer. Material and methods: The peripheral blood samples of 6 clinically healthy adults were tested in triplicate according to the manufacturer recommendations. The intraassay imprecision as well as the ranges of neutrophil and monocyte burst activation triggered by various stimuli were assessed. Results: The activation range of granulocytes and monocytes was similar to the one described by the producer in the presence of E. coli (granulocytes: 78.45-99.43% versus 99.6-99.95%, average %CV of 1.53% versus 0.1%, monocytes: 54.63-92.33% versus 81.80-96.67, average %CV 6.92% versus 1.1%). The leukocyte range of activation in the presence of non-opsonized C. albicans was comparable to the one triggered by the fMLP (N-formyl-methionyl-leucyl-phenylalanine) stimulus. Conclusion: The intra-assay precision obtained in our laboratory conditions, as well as the ranges of activated leukocytes, are comparable to the ones described by the producer when using E. coli as a stimulus. The present study shows that introducing an extra fungal stimulus for burst oxidation assessment could provide additional information regarding the non-specific cellular immune response, particularly in patients at risk for candidemia. Keywords: flow cytometry, method verification, intra-assay precision, reactive oxygen species, fungal bloodstream infection Received 23 April 2017 / Accepted 4 June 2017 IntroductionThe peripheral blood phagocytes (PBP) have long been acknowledged as key factors in bacterial and fungal infections. As first line of defense, they phagocyte and kill microorganisms through a combination of mechanisms that include the production of reactive oxygen species (ROS) [1].Along the years, flow cytometry methods have been developed in order to quantify the production of ROS using bacteria as stimulus [2,3]. Different authors have described methods for burst oxidation assessment in peripheral blood mononuclear cells (PBMC) using isolated leukocytes and different strains of Candida as stimuli as well as different incubation periods [4][5][6][7][8]. Recent years have seen the development of several commercial kits that use whole blood, not isolated PBMC as many methods used before, and unlabeled opsonized Escherichia coli as stimulus for PBP activation besides other chemical stimulants [9]. Up to the present moment none of the available commercial kits used fungi as stimulus.The aim of the present study was to verify in our laboratory conditions the performance criteria of the commercial kit Phagoburst TM (Glycotope Biotechnology) as recommended by the producers. We have also partially altered the use of the available kit by introducing a non-opsoniz...

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“…The current study confirms the presence of these host proteins on devices from various niches and points to the similarities between the biofilm infection models and common device-associated clinical infections. C. albicans is known to interact with these ubiquitous matricellular proteins through specific interactions, which may enhance tissue invasion and contribute to virulence (43)(44)(45)(46)(47)(48)(49)(50)(51)(52)(53)(54). Given the evidence for the likely involvement of these proteins in Candida pathogenicity, pioneering biofilm investigations have emphasized the importance of a host conditioning fluid for optimal biofilm formation and the need to account for the proteins in in vitro biofilm models (29,35,(55)(56)(57)(58).…”

Section: Discussionmentioning

confidence: 99%

Host Contributions to Construction of Three Device-Associated Candida albicans Biofilms

et al. 2015

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e Among the most fascinating virulence attributes of Candida is the ability to transition to a biofilm lifestyle. As a biofilm, Candida cells adhere to a surface, such as a vascular catheter, and become encased in an extracellular matrix. During this mode of growth, Candida resists the normal immune response, often causing devastating disease. Based on scanning electron microscopy images, we hypothesized that host cells and proteins become incorporated into clinical biofilms. As a means to gain an understanding of these host-biofilm interactions, we explored biofilm-associated host components by using microscopy and liquid chromatography-mass spectrometry. Here we characterize the host proteins associated with several in vivo rat Candida albicans biofilms, including those from vascular catheter, denture, and urinary catheter models as well as uninfected devices. A conserved group of 14 host proteins were found to be more abundant during infection at each of the niches. The host proteins were leukocyte and erythrocyte associated and included proteins involved in inflammation, such as C-reactive protein, myeloperoxidase, and alarmin S100-A9. A group of 59 proteins were associated with both infected and uninfected devices, and these included matricellular and inflammatory proteins. In addition, site-specific proteins were identified, such as amylase in association with the denture device. Cellular analysis revealed neutrophils as the predominant leukocytes associating with biofilms. These experiments demonstrate that host cells and proteins are key components of in vivo Candida biofilms, likely with one subset associating with the device and another being recruited by the proliferating biofilm.

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Candida albicans Uses the Surface Protein Gpm1 to Attach to Human Endothelial Cells and to Keratinocytes via the Adhesive Protein Vitronectin

Cited by 57 publications

References 58 publications

Network of Surface-Displayed Glycolytic Enzymes in Mycoplasma pneumoniae and Their Interactions with Human Plasminogen

Network of Surface-Displayed Glycolytic Enzymes in Mycoplasma pneumoniae and Their Interactions with Human Plasminogen

Flow Cytometry Assessment of Bacterial and Yeast Induced Oxidative Burst in Peripheral Blood Phagocytes

Host Contributions to Construction of Three Device-Associated Candida albicans Biofilms

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