scholarly journals Fibronectin‐Binding Proteins and Fibrinogen‐Binding Clumping Factors Play Distinct Roles in Staphylococcal Arthritis and Systemic Inflammation

2005 ◽  
Vol 191 (5) ◽  
pp. 791-798 ◽  
Author(s):  
Niklas Palmqvist ◽  
Timothy Foster ◽  
J. Ross Fitzgerald ◽  
Elisabet Josefsson ◽  
Andrzej Tarkowski
Keyword(s):  
Systemic Inflammation ◽  
Binding Proteins ◽  
Fibrinogen Binding ◽  
Fibronectin Binding

scholarly journals A Novel Staphylococcus aureus Biofilm Phenotype Mediated by the Fibronectin-Binding Proteins, FnBPA and FnBPB

2008 ◽  
Vol 190 (11) ◽  
pp. 3835-3850 ◽  
Author(s):  
Eoghan O'Neill ◽  
Clarissa Pozzi ◽  
Patrick Houston ◽  
Hilary Humphreys ◽  
D. Ashley Robinson ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Biofilm Formation ◽  
Binding Proteins ◽  
Clinical Problem ◽  
Growth Conditions ◽  
Surface Proteins ◽  
Fibrinogen Binding ◽  
Fibronectin Binding ◽  
Mrsa Strains ◽  
Biofilm Development

ABSTRACT Device-associated infections involving biofilm remain a persistent clinical problem. We recently reported that four methicillin-resistant Staphylococcus aureus (MRSA) strains formed biofilm independently of the icaADBC-encoded exopolysaccharide. Here, we report that MRSA biofilm development was promoted under mildly acidic growth conditions triggered by the addition of glucose to the growth medium. Loss of sortase, which anchors LPXTG-containing proteins to peptidoglycan, reduced the MRSA biofilm phenotype. Furthermore introduction of mutations in fnbA and fnbB, which encode the LPXTG-anchored multifunctional fibrinogen and fibronectin-binding proteins, FnBPA and FnBPB, reduced biofilm formation by several MRSA strains. However, these mutations had no effect on biofilm formation by methicillin-sensitive S. aureus strains. FnBP-promoted biofilm occurred at the level of intercellular accumulation and not primary attachment. Mutation of fnbA or fnbB alone did not substantially affect biofilm, and expression of either gene alone from a complementing plasmid in fnbA fnbB mutants restored biofilm formation. FnBP-promoted biofilm was dependent on the integrity of SarA but not through effects on fnbA or fnbB transcription. Using plasmid constructs lacking regions of FnBPA to complement an fnbAB mutant revealed that the A domain alone and not the domain required for fibronectin binding could promote biofilm. Additionally, an A-domain N304A substitution that abolished fibrinogen binding did not affect biofilm. These data identify a novel S. aureus biofilm phenotype promoted by FnBPA and FnBPB which is apparently independent of the known ligand-binding activities of these multifunctional surface proteins.

scholarly journals Dissociation Rate Constants of Human Fibronectin Binding to Fibronectin-binding Proteins on LivingStaphylococcus aureusIsolated from Clinical Patients

2012 ◽  
Vol 287 (9) ◽  
pp. 6693-6701 ◽  
Author(s):  
Nadia N. Casillas-Ituarte ◽  
Brian H. Lower ◽  
Supaporn Lamlertthon ◽  
Vance G. Fowler ◽  
Steven K. Lower
Keyword(s):  
Rate Constants ◽  
Binding Proteins ◽  
Dissociation Rate ◽  
Human Fibronectin ◽  
Fibronectin Binding ◽  
Dissociation Rate Constants

scholarly journals Protein F1 and Streptococcus pyogenes Resistance to Phagocytosis

2007 ◽  
Vol 75 (6) ◽  
pp. 3188-3191 ◽  
Author(s):  
Kendra A. Hyland ◽  
Beinan Wang ◽  
P. Patrick Cleary
Keyword(s):  
Epithelial Cells ◽  
Protein Expression ◽  
Streptococcus Pyogenes ◽  
Binding Proteins ◽  
M Protein ◽  
Partial Inhibition ◽  
Fibronectin Binding ◽  
Negative Mutant

ABSTRACT Streptococcus pyogenes is a major cause of pharyngitis in humans and encodes several fibronectin-binding proteins. M protein and protein F1 (PrtF1/SfbI) are differentially regulated by CO2 and O2, respectively, and both mediate the invasion of epithelial cells. This study examined whether PrtF1/SfbI shares other properties with M protein. Expression of the PrtF1/SfbI protein by an M-negative mutant conferred resistance to phagocytosis and partial inhibition of C3 deposition on the S. pyogenes surface.

scholarly journals Fibronectin binding to thrombin-stimulated platelets: evidence for fibrin(ogen) independent and dependent pathways

Blood ◽  
1985 ◽  
Vol 66 (1) ◽  
pp. 26-32
Author(s):  
EF Plow ◽  
GA Marguerie ◽  
MH Ginsberg
Keyword(s):  
Molecular Weight ◽  
Acetic Acid ◽  
Living Cells ◽  
Plasma Fibronectin ◽  
Divalent Ions ◽  
Fibrinogen Binding ◽  
Calcium Requirement ◽  
Variable Extent ◽  
Fibronectin Binding ◽  
Dependent Pathway

Plasma fibronectin binds in a specific and saturable manner to thrombin- stimulated platelets. gamma-Thrombin stimulated 80% as much fibronectin binding to platelets as alpha-thrombin with conversion of less than or equal to 1% of platelet fibrinogen to fibrin. Afibrinogenemic and normal platelets bound similar quantities of fibronectin in the presence of calcium or magnesium-ethylene glycol tetra-acetic acid (EGTA). These observations indicate that fibronectin can interact with platelets without involvement of fibrin or fibrinogen. Nevertheless, two different effects of fibrin(ogen) on fibronectin binding were observed. First, exogenous fibrinogen inhibited fibronectin binding to thrombin-stimulated platelets. This inhibition was unidirectional, as fibronectin did not inhibit fibrinogen binding to ADP or thrombin- stimulated cells. Second, formaldehyde-fixed cells with surface- associated fibrin bound significant quantities of fibronectin. This interaction required calcium and did not occur on fixed cells with or without surface-bound fibrinogen. A portion of the ligand bound to fixed cells with surface-associated fibrin was modified to form a derivative with a molecular weight identical to that of the fibronectin subunit cross-linked to the alpha-chain of fibrin. This high mol wt derivative was also observed to a variable extent with living cells in the presence of magnesium or calcium but not in the presence of magnesium-EGTA. Thus, fibronectin binds to platelets by at least two mechanisms: (1) a fibrin(ogen)-independent pathway that requires divalent ions and is inhibited by exogenous fibrinogen; and (2) a fibrin-dependent pathway with an absolute calcium requirement. With nonaggregated, thrombin-stimulated platelets, the former pathway appears to predominate.

Role for the fibrinogen-binding proteins Coagulase and Efb in the Staphylococcus aureus–Candida interaction

2013 ◽  
Vol 303 (5) ◽  
pp. 230-238 ◽  
Author(s):  
Carsten Fehrmann ◽  
Kerstin Jurk ◽  
Anne Bertling ◽  
Gabriela Seidel ◽  
Wolfgang Fegeler ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Binding Proteins ◽  
Fibrinogen Binding

scholarly journals The FasX Small Regulatory RNA Negatively Regulates the Expression of Two Fibronectin-Binding Proteins in Group A Streptococcus

2015 ◽  
Vol 197 (23) ◽  
pp. 3720-3730 ◽  
Author(s):  
Jessica L. Danger ◽  
Nishanth Makthal ◽  
Muthiah Kumaraswami ◽  
Paul Sumby
Keyword(s):  
Cell Surface ◽  
Virulence Factors ◽  
Binding Proteins ◽  
Mrna Translation ◽  
Regulatory Rna ◽  
Collagen Binding ◽  
Content Type ◽  
Small Regulatory Rna ◽  
Group A ◽  
Fibronectin Binding

ABSTRACTThe group AStreptococcus(GAS;Streptococcus pyogenes) causes more than 700 million human infections each year. The success of this pathogen can be traced in part to the extensive arsenal of virulence factors that are available for expression in temporally and spatially specific manners. To modify the expression of these virulence factors, GAS use both protein- and RNA-based regulators, with the best-characterized RNA-based regulator being the small regulatory RNA (sRNA) FasX. FasX is a 205-nucleotide sRNA that contributes to GAS virulence by enhancing the expression of the thrombolytic secreted virulence factor streptokinase and by repressing the expression of the collagen-binding cell surface pili. Here, we have expanded the FasX regulon, showing that this sRNA also negatively regulates the expression of the adhesion- and internalization-promoting, fibronectin-binding proteins PrtF1 and PrtF2. FasX posttranscriptionally regulates the expression of PrtF1/2 through a mechanism that involves base pairing to theprtF1andprtF2mRNAs within their 5′ untranslated regions, overlapping the mRNA ribosome-binding sites. Thus, duplex formation between FasX and theprtF1andprtF2mRNAs blocks ribosome access, leading to an inhibition of mRNA translation. Given that FasX positively regulates the expression of the spreading factor streptokinase and negatively regulates the expression of the collagen-binding pili and of the fibronectin-binding PrtF1/2, our data are consistent with FasX functioning as a molecular switch that governs the transition of GAS between the colonization and dissemination stages of infection.IMPORTANCEMore than half a million deaths each year are a consequence of infections caused by GAS. Insights into how this pathogen regulates the production of proteins during infection may facilitate the development of novel therapeutic or preventative regimens aimed at inhibiting this activity. Here, we have expanded insight into the regulatory activity of the GAS small RNA FasX. In addition to identifying that FasX reduces the abundance of the cell surface-located fibronectin-binding proteins PrtF1/2, fibronectin is present in high abundance in human tissues, and we have determined the mechanism behind this regulation. Importantly, as FasX is the only mechanistically characterized regulatory RNA in GAS, it serves as a model RNA in this and related pathogens.

scholarly journals Increased Virulence of a Fibronectin-Binding Protein Mutant of Staphylococcus aureus in a Rat Model of Pneumonia

2002 ◽  
Vol 70 (7) ◽  
pp. 3865-3873 ◽  
Author(s):  
Mary C. McElroy ◽  
David J. Cain ◽  
Christine Tyrrell ◽  
Timothy J. Foster ◽  
Christopher Haslett
Keyword(s):  
Staphylococcus Aureus ◽  
Epithelial Cells ◽  
Rat Model ◽  
Binding Proteins ◽  
Binding Protein ◽  
Alveolar Epithelial Cells ◽  
Alveolar Epithelial ◽  
Fibronectin Binding Protein ◽  
Fibronectin Binding

ABSTRACT Fibronectin-binding proteins mediate Staphylococcus aureus internalization into nonphagocytic cells in vitro. We have investigated whether fibronectin-binding proteins are virulence factors in the pathogenesis of pneumonia by using S. aureus strain 8325-4 and isogenic mutants in which fibronectin-binding proteins were either deleted (DU5883) or overexpressed [DU5883(pFnBPA4)]. We first demonstrated that fibronectin-binding proteins mediate S. aureus internalization into alveolar epithelial cells in vitro and that S. aureus internalization into alveolar epithelial cells requires actin rearrangement and protein kinase activity. Second, we established a rat model of S. aureus-induced pneumonia and measured lung injury and bacterial survival at 24 and 96 h postinoculation. S. aureus growth and the extent of lung injury were both increased in rats inoculated with the deletion mutant (DU5883) in comparison with rats inoculated with the wild-type (8325-4) and the fibronectin-binding protein-overexpressing strain DU5883(pFnBPA4) at 24 h postinfection. Morphological evaluation of infected lungs at the light and electron microscopic levels demonstrated that S. aureus was present within neutrophils from both 8325-4- and DU5883-inoculated lungs. Our data suggest that fibronectin-binding protein-mediated internalization into alveolar epithelial cells is not a virulence mechanism in a rat model of pneumonia. Instead, our data suggest that fibronectin-binding proteins decrease the virulence of S. aureus in pneumonia.

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