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Query: UMLS:C0014118 (endocarditis)
 15,629 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A new mouse model of locally induced osteomyelitis was used to study the importance for pathogenicity of the specific binding ability of Staphylococcus aureus to collagen and fibronectin. This method appears to be convenient, reproducible, and suitable for large-scale experiments. In contrast to previous studies in experimental arthritis and endocarditis models, no difference in infection rates was found between the strains deficient in binding to collagen compared with the corresponding adherence-proficient strains. However, fibronectin binding ability in this model, in contrast to the endocarditis model, is thought to enhance the microorganisms' capacity to establish an infection. Infections caused by the fibronectin-binding strain also are thought to be clinically more aggressive than those caused by the nonbinding strain. Specific adherence mechanisms are thought to be operative in the pathogenesis of biomaterial associated osteomyelitis, and an improved understanding of such mechanisms may have an important prophylactic and therapeutic impact.
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PMID:Collagen and fibronectin binding in experimental staphylococcal osteomyelitis. 1115 94

Staphylococcus aureus bacteraemia (SAB) originating from local infections can lead to severe secondary infections such as endocarditis. The protective effect of antibodies against secondary infections was studied in a rat model, where a local joint infection leads to bacteraemia and endocarditis on damaged aortic valves. In this study, immunizations with a truncated D2-domain of the S. aureus fibronectin-binding protein displayed on a cow-pea mosaic virus (CPMV-D) carrier induced protection against endocarditis (P < 0.05). Opsonization of S. aureus with antibodies raised against CPMV-D stimulated both neutrophil activity and macrophage phagocytosis in vitro. Furthermore, intravenous administration of these antibodies protected mice from weight loss due to SAB.
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PMID:Antibodies against a truncated Staphylococcus aureus fibronectin-binding protein protect against dissemination of infection in the rat. 1134 1

Since Staphylococcus aureus expresses multiple pathogenic factors, studying their individual roles in single-gene-knockout mutants is difficult. To circumvent this problem, S. aureus clumping factor A (clfA) and fibronectin-binding protein A (fnbA) genes were constitutively expressed in poorly pathogenic Lactococcus lactis using the recently described pOri23 vector. The recombinant organisms were tested in vitro for their adherence to immobilized fibrinogen and fibronectin and in vivo for their ability to infect rats with catheter-induced aortic vegetations. In vitro, both clfA and fnbA increased the adherence of lactococci to their specific ligands to a similar extent as the S. aureus gene donor. In vivo, the minimum inoculum size producing endocarditis in > or =80% of the rats (80% infective dose [ID80]) with the parent lactococcus was > or =10(7) CFU. In contrast, clfA-expressing and fnbA-expressing lactococci required only 10(5) CFU to infect the majority of the animals (P < 0.00005). This was comparable to the infectivities of classical endocarditis pathogens such as S. aureus and streptococci (ID80 = 10(4) to 10(5) CFU) in this model. The results confirmed the role of clfA in endovascular infection, but with a much higher degree of confidence than with single-gene-inactivated staphylococci. Moreover, they identified fnbA as a critical virulence factor of equivalent importance. This was in contrast to previous studies that produced controversial results regarding this very determinant. Taken together, the present observations suggest that if antiadhesin therapy were to be developed, at least both of the clfA and fnbA products should be blocked for the therapy to be effective.
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PMID:Reassessing the role of Staphylococcus aureus clumping factor and fibronectin-binding protein by expression in Lactococcus lactis. 1155 73

The mechanisms of bacterial adherence in the initial stages of native valve endocarditis are unclear, especially in patients without valve disease or the presence of a platelet-fibrin thrombus. Extracellular matrix may act as a ligand in areas of exposed basement membrane on the endothelial monolayer. In this study, adherence of 55 clinical blood and 21 oral viridans streptococcal isolates was examined using purified extracellular matrix compounds. The majority of blood and oral isolates exhibited adherence to purified laminin, fibronectin, and fibrinogen, with lesser adherence to type I and IV collagens. Adherence to laminin and fibronectin was concentration dependent, saturable, and competitively inhibited with soluble ligand. A Streptococcus anginosus isolate and other viridans strains exhibiting a strong laminin adherence phenotype bound extensively to the endothelial aspect of human and porcine valve tissue sections and were inhibited by soluble laminin and anti-laminin antibody fragments. Using a novel native porcine valve explant adherence model, we localized binding to areas of exposed basement membrane by confocal and scanning electron microscopy. These studies support the hypothesis that bacterial adherence to exposed basement membrane plays a role in the initial phase of native valve endocarditis.
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PMID:Streptococcus anginosus adheres to vascular endothelium basement membrane and purified extracellular matrix proteins. 1207 9

Aspirin has been shown to cause a reduction in the virulence of Staphylococcus aureus-associated endocarditis. A new study reveals that salicylic acid, the major metabolite of aspirin, acts at the level of transcription to downregulate the production of fibrinogen, fibronectin, and alpha-hemolysin - virulence factors necessary for bacterial replication in host tissues and, now, potential therapeutic targets.
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PMID:Salicylic acid: an old dog, new tricks, and staphylococcal disease. 1286 10

Aspirin has been previously shown to reduce the in vivo virulence of Staphylococcus aureus in experimental endocarditis, through antiplatelet and antimicrobial mechanisms. In the present study, salicylic acid, the major in vivo metabolite of aspirin, mitigated two important virulence phenotypes in both clinical and laboratory S. aureus strains: alpha-hemolysin secretion and fibronectin binding in vitro. In addition, salicylic acid reduced the expression of the alpha-hemolysin gene promoter, hla, and the fibronectin gene promoter, fnbA. Transcriptional analysis, fluorometry, and flow cytometry revealed evidence of salicylic acid-mediated activation of the stress-response gene sigB. Expression of the sigB-repressible global regulon sarA and the global regulon agr were also mitigated by salicylic acid, corresponding to the reduced expression of the hla and fnbA genes in vitro. Studies in experimental endocarditis confirmed the key roles of both sarA and sigB in mediating the antistaphylococcal effects of salicylic acid in vivo. Therefore, aspirin has the potential to be an adjuvant therapeutic agent against endovascular infections that result from S. aureus, by downmodulating key staphylococcal global regulons and structural genes in vivo, thus abrogating relevant virulence phenotypes.
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PMID:Salicylic acid attenuates virulence in endovascular infections by targeting global regulatory pathways in Staphylococcus aureus. 1286 3

A gene encoding a major secreted antigen, SagA, was identified in Enterococcus faecium by screening an E. faecium genomic expression library with sera from patients with E. faecium-associated endocarditis. Recombinant SagA protein showed broad-spectrum binding to extracellular matrix (ECM) proteins, including fibrinogen, collagen type I, collagen type IV, fibronectin, and laminin. A fibrinogen-binding protein, purified from culture supernatants of an E. faecium clinical isolate, was found to match the N-terminal sequence of the predicted SagA protein and to react with the anti-SagA antibody, confirming that it was the SagA protein; this protein appeared as an 80- to 90-kDa smear on a Western blot that was sensitive to proteinase K and resistant to periodate treatment and glycoprotein staining. When overexpressed in E. faecium and Escherichia coli, the native and recombinant SagA proteins formed stable oligomers, apparently via their C-terminal domains. The SagA protein is composed of three domains: (i) a putative coiled-coil N-terminal domain that shows homology to the N-terminal domain of Streptococcus mutans SagA protein (42% similarity), previously shown to be involved in cell wall integrity and cell shape maintenance, and to the P45 protein of Listeria monocytogenes (41% similarity); (ii) a central domain containing direct repeats; and (iii) a C-terminal domain that is similar to that found in various proteins, including P45 (50% similarity) and P60 (52% similarity) of L. monocytogenes. The P45 and P60 proteins both have cell wall hydrolase activity, and the latter has also been shown to be involved in virulence, whereas cell wall hydrolase activity was not detected for SagA protein. The E. faecium sagA gene, like the S. mutans homologue, is located in a cluster of genes encoding proteins that appear to be involved in cell wall metabolism and could not be disrupted unless it was first transcomplemented, suggesting that the sagA gene is essential for E. faecium growth and may be involved in cell wall metabolism. In conclusion, the extracelluar E. faecium SagA protein is apparently essential for growth, shows broad-spectrum binding to ECM proteins, forms oligomers, and is antigenic during infection.
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PMID:An Enterococcus faecium secreted antigen, SagA, exhibits broad-spectrum binding to extracellular matrix proteins and appears essential for E. faecium growth. 1293 46

We have developed a multiplex PCR procedure to determine the distribution of nine adhesin genes in Staphylococcus aureus isolates. Only genes encoding bone sialoprotein binding protein and fibronectin binding protein B were significantly associated with hematogenous osteomyelitis/arthritis and native-valve endocarditis, respectively, suggesting their involvement in hematogenous tissue infections.
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PMID:Use of multiplex PCR to identify Staphylococcus aureus adhesins involved in human hematogenous infections. 1295 96

The fibronectin (Fn)-binding ability of microorganisms is considered to be involved in their pathogenicities. Granulicatella adiacens, a member of the oral flora and a causative agent of culture-negative infective endocarditis, showed nearly maximum binding to immobilized Fn at pH 7.2 but greatly reduced binding at a slightly higher pH 7.4 and almost no binding at pH 7.6 in the presence of physiological concentration of NaCl (0.15 M). A similar pH-sensitive Fn-binding property was noted with Escherichia coli and Abiotrophia defectiva, but not with Streptococcus pyogenes nor Staphylococcus aureus. In contrast, bindings to laminin and fibrinogen observed for some of these strains were unaffected by the same pH changes. This fastidious pH-dependency of Fn-binding abilities of some bacteria warns that the pH condition must be seriously considered in the in vitro assay of bacterial adherence to fibronectin.
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PMID:Inhibition of fibronectin binding of some bacterial cells by subtle pH increase within the physiological range. 1449 92

We investigated the impacts of sarA and agr on fnbA expression and fibronectin-binding capacity in Staphylococcus aureus in vitro and in experimental endocarditis. Although sarA up-regulated and agr down-regulated both fnbA expression and fibronectin binding in vitro and in vivo, fnbA expression was positively regulated in the absence of both global regulators. Thus, additional regulatory loci contribute to fnbA regulation and fibronectin-binding capacities in S. aureus.
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PMID:Impacts of sarA and agr in Staphylococcus aureus strain Newman on fibronectin-binding protein A gene expression and fibronectin adherence capacity in vitro and in experimental infective endocarditis. 1497 98


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