Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0014118 (endocarditis)
 15,629 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Antibody responses to staphylococcal alpha-toxin, cell wall teichoic acid, and cell wall peptidoglycan were measured in 259 serum samples from 74 consecutive patients with Staphylococcus aureus bacteremia. All patients with complicated bacteremia were seropositive in at least one of three tests, and 18 (72%) of 25 were positive in two or three assays; six (75%) of eight patients with endocarditis were positive for all three tests. In contrast, 15 (75%) of 20 patients with uncomplicated bacteremia were positive in only one or none of the tests. These differences in antibody response patterns were statistically significant (chi 2 = 18.33, P less than .001). Patients with complicated bacteremia had peak antibody titers that were significantly higher than those of patients with uncomplicated bacteremia. The assay for antibody to alpha-toxin was as sensitive as the assays for antibody to cell wall antigens but had less specificity for complicated bacteremia. The clinical severity of the bacteremia did not correlate with a complicated vs. uncomplicated nature of the infection but was predictive of early death due to staphylococcemia. The calculated predictive values suggest that the serology of S. aureus bacteremia may be clinically valuable when multiple tests are performed in paired serum samples.
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PMID:Distinguishing complicated from uncomplicated bacteremia caused by Staphylococcus aureus: the value of "new" and "old" serological tests. 394 Dec 74

An enzyme-linked immunosorbent assay (ELISA) was used with a purified alpha-toxin preparation to measure the serum IgG, IgM and IgA response in staphylococcal septicaemia and endocarditis. ELISA for IgG antibodies against alpha-toxin was found to be more sensitive than the neutralization test (ASTA). IgM and IgA antibody determination was found to be of limited diagnostic value. A correlation between IgG antibodies to alpha-toxin and purified beta-toxin was found in ELISA, although antibody determination to beta-toxin was a less sensitive diagnostic method. The highest diagnostic sensitivity in deep staphylococcal infections was obtained by parallel performance of ELISA to alpha-toxin and purified teichoic acid. By this approach, 32/35 (91%) patients with endocarditis, 12/14 (86%) with complicated septicaemia and 15/22 (68%) with uncomplicated septicaemia showed increased titres in samples drawn between days 7-30 of disease. Diagnostic sensitivity was further increased to 31/32 (97%) positive patients, when paired or multiple samples from patients with septicaemic staphylococcal disease were analysed.
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PMID:Serological diagnosis of deep Staphylococcus aureus infections by enzyme-linked immunosorbent assay (ELISA) for staphylococcal hemolysins and teichoic acid. 637 58

In comparison to healthy controls we have found that patients with endocarditis and septicaemia caused by Staphylococcus aureus show significantly higher antibody levels against either S. aureus peptidoglycan, crude staphylococcal antigen or alpha-toxin. The serological methods used in these studies were radio-immunoassays. These results have now been further evaluated concerning their clinical significance. The occurrence rate of S. aureus endocarditis and septicaemia at the clinic was 0.36% and 2.0%, respectively, during the study period. In spite of relatively high levels of test specificities, 93.8-96.9%, the predictive values for positive test results were low, 2.7-23.2%. Using the PG-assay, satisfactory predictive values of 100% together with a sensitivity of 95.2% could nevertheless be reached in the screening for S. aureus endocarditis, if the upper normal limit was raised.
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PMID:The clinical significance of serological methods in the diagnosis of staphylococcal septicaemia and endocarditis. 658 49

An enzyme-linked immunosorbent assay (ELISA) was used with purified alpha-toxin and teichoic acid preparations to measure the IgG and IgM response in Staphylococcus aureus infections. After determining antibodies in a normal population, cut-off levels were set for all age groups. ELISA with alpha-toxin was more sensitive than the antistaphylolysin neutralization test (ASTA). Determining IgM antibodies with the two antigens was found to be of limited diagnostic value. Positive IgG titers against alpha-toxin were found in 21 of 27 patients (78%) with endocarditis, 11 of 14 (79%) with complicated septicemia, eight of 20 (40%) with uncomplicated septicemia and in 12 of 22 (54%) with chronic osteomyelitis. The IgG responses to teichoic acid and alpha-toxin were somewhat different when measured by ELISA, and the parallel performance of the two assays resulted in improved serological diagnostics. The number of positive patients increased to 89%, 86%, 65% and 64%, respectively, in the four groups with a diagnostic specificity of 93%. In septicemic staphylococcal infections, the diagnosis could be established in all patients (28 of 28) with adequately spaced paired samples.
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PMID:The role of antibodies against alpha-toxin and teichoic acid in the diagnosis of staphylococcal infections. 686 37

The gene encoding alpha-toxin from Staphylococcus aureus was cloned into a Bacillus subtilis expression vector (pEF 231/alpha-Tox). The protease-deficient B. subtilis strain DB 104 transformed with pEF 231/alpha-Tox expressed and secreted 5 mg of alpha-toxin per liter into the growth medium. The alpha-toxin-containing supernatant was diluted 200-fold and used as coating antigen in an enzyme-linked immunosorbent assay (ELISA) for serodiagnosis of septicemia and endocarditis caused by S. aureus. Paired sera from patients in acute and convalescent stages of S. aureus and non-S. aureus infections were used to evaluate this ELISA. To evaluate the effectiveness of the crude preparation, the results were compared with those of an ELISA based on a commercially available alpha-toxin. Similar rises in serum titers were obtained with either type of alpha-toxin preparation. This is the first time a crude supernatant without any further purification has been used as an ELISA coating antigen. We therefore conclude that B. subtilis is a suitable host organism for cheap and simple production of prokaryotic recombinant antigens to be used in serodiagnosis.
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PMID:Evaluation of new enzyme-linked immunosorbent assay based on a supernatant containing Staphylococcus aureus alpha-toxin produced by Bacillus subtilis. 826 93

Staphylococcal alpha-toxin targets several cell types which are important components of cardiac vegetations in endocarditis, including platelets, erythrocytes, and endothelial cells. We evaluated the in vivo role of Staphylococcus aureus alpha-toxin in experimental endocarditis by using isogenic strains differing in the capacity to produce functional alpha-toxin, including 8325-4 (wild-type strain), DU-1090 (a mutant strain with allelic replacement of the alpha-toxin gene [hla]), DU1090(pH35L) (a mutant strain producing a target cell-binding but nonlytic toxin), DU1090(pDU1212) (a variant of DU1090 carrying the cloned hla gene on a multicopy plasmid), and DU1090(pCL84::hla) (a variant of DU1090 with a single copy of the hla gene cloned into the chromosomal lipase locus). In vitro, wild-type alpha-toxin (from parental strain 8325-4) extensively lysed both erythrocytes and platelets. In contrast, mutant alpha-toxin [from strain DU1090(pH35L)] lysed neither cell type. Following exposure to the wild-type alpha-toxin, platelet lysates were found to contain microbicidal activity against Bacillus subtilis (but not against Micrococcus luteus), as well as against the parental and alpha-toxin variant S. aureus strains noted above. Furthermore, lysate microbicidal activity was heat stable, neutralized by polyanionic filters or compounds, and recoverable from anionic filter membranes by hypertonic saline elution. These characteristics are consistent with those of cationic platelet microbicidal proteins (PMPs). Reverse-phase high-pressure liquid chromatography and polyacrylamide gel electrophoresis confirmed the presence of three distinct PMPs (1, 2, and 3) in platelet lysates. In experimental endocarditis, the two variant staphylococcal strains producing either minimal alpha-toxin or nonlytic alpha-toxin in vitro [strains DU1090 and DU1090(pH35L), respectively] exhibited significantly lower virulence in vivo than the parental strain (decreased intravegetation staphylococcal densities). Paradoxically, the two variant staphylococcal strains producing alpha-toxin at supraparental levels in vitro [strains DU1090(p1212) and DU1090(pCL84::hla)] also exhibited significantly decreased induction rates and intravegetation staphylococcal densities in experimental endocarditis versus the parental strain. The reduced in vivo virulence of the latter variant staphylococcal strains could not be explained by differences in bacteremic clearance or initial adherence to sterile vegetations (compared to the parental strain). These findings suggest that the reduced virulence exhibited by the variant staphylococcal strains in this model was related to pathogenetic events subsequent to bacterial adherence to the damaged endocardium. Excess intravegetation secretion of alpha-toxin, leading to increased PMP release (secondary to either increased platelet secretion or lysis), may well explain the reduced virulence observed in experimental endocarditis.
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PMID:Hyperproduction of alpha-toxin by Staphylococcus aureus results in paradoxically reduced virulence in experimental endocarditis: a host defense role for platelet microbicidal proteins. 935 46

It is now generally accepted that adherence of microorganisms to various components of cardiac valve surfaces or vegetation lodging on the heart valves is an important early event in the pathogenesis of infective endocarditis. 120 clinical isolates of S. aureus obtained from patients with endocarditis and wound infections and from nasopharyngeal carriers were quantitatively analysed in vitro for their ability to bind to fibronectin and to produce protein A and alpha-toxin. Both cell-bound and extracellular protein A were measured and alpha-toxin was determined as antigen and as haemolytic activity. The highest fibronectin binding ability was found in carrier strains while no significant differences between strains were observed regarding the production of protein A. Strains isolated from patients with endocarditis produced significantly lower amounts of alpha-toxin than did strains from the other two groups. An inverse relationship between the production of protein A and of alpha-toxin was noticed in the material. Animal passage of five strains in an experimental endocarditis model showed a good reproducibility of the test systems and one strain was upregulated in its fibronectin binding ability and in alpha-toxin production. These in vitro results indicate that the fibronectin binding ability is not the decisive adherence factor and question the role of alpha-toxin as a virulence factor in endocarditis.
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PMID:Virulence factors of Staphylococcus aureus in the pathogenesis of endocarditis. A comparative study of clinical isolates. 963 73

Bacterial recognition of host sialic acid-containing receptors plays an important role in microbial colonization of the human oral cavity. The aggregation of human platelets by Streptococcus gordonii DL1 is implicated in the pathogenesis of infective endocarditis. In addition, we consider that hemagglutination of this organism may act as an additive factor to increase the severity of this disease. We previously reported that this interaction requires the bacterial expression of a 203-kDa protein (Hsa), which has sialic acid-binding activity. In the present study, we confirmed that erythrocyte surface sialoglycoproteins are the receptors for Hsa. We examined the effects of proteinase K, chymotrypsin, phospholipase C, and alpha(2-3) or alpha(2-3, 6, 8) neuraminidase on hemagglutination activity and found that the interaction occurs between Hsa and alpha2-3-linked sialic acid-containing proteins of erythrocytes. We expressed recombinant NR2, which is the putative binding domain of Hsa, fused with GST in Escherichia coli BL21. Dot-blot analysis demonstrated that GST-HsaNR2 binds both glycophorin A (GPA) and band 3. Moreover, GPA and a small amount of band 3 were detected by GST pull-down assays. These findings indicate that S. gordonii Hsa specifically binds to GPA and band 3, alpha2-3-linked sialic acid membrane glycoproteins.
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PMID:Hsa, an adhesin of Streptococcus gordonii DL1, binds to alpha2-3-linked sialic acid on glycophorin A of the erythrocyte membrane. 1838 Aug 4

Staphylococcus aureus is a major cause of community-acquired and nosocomial infections including the life-threatening conditions endocarditis, necrotizing pneumonia, necrotizing fasciitis, and septicemia. Toll-like receptor (TLR)-2, a membrane-bound microbial sensor, detects staphylococcal components, but macrophages lacking TLR2 or both TLR2 and TLR4 remain S. aureus responsive, suggesting that an alternative microbial recognition receptor might be involved. The cytoplasmic sensor nucleotide-binding oligomerization domain containing (NOD) 2/caspase recruitment domain (CARD) 15 detects muramyl dipeptide from bacterial peptidoglycans and mediates cytokine responses to S. aureus in vitro, but the physiological significance of these observations is not well defined. Here we show that NOD2-deficient mice exhibit a delayed but ultimately exacerbated ulcerative response and impaired bacterial clearance after s.c. infection with S. aureus. NOD2-dependent recognition of S. aureus and muramyl dipeptide is facilitated by alpha-toxin (alpha-hemolysin), a pore-forming toxin and virulence factor of the pathogen. The action of NOD2 is dependent on IL-1beta-amplified production of IL-6, which promotes rapid bacterial killing by neutrophils. These results significantly broaden the physiological importance of NOD2 in innate immunity from the recognition of bacteria that primarily enter the cytoplasm to the detection of bacteria that typically reside extracellularly and demonstrate that this microbial sensor contributes to the discrimination between commensal bacteria and bacterial pathogens that elaborate pore-forming toxins.
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PMID:NOD2 contributes to cutaneous defense against Staphylococcus aureus through alpha-toxin-dependent innate immune activation. 1954 30

The SaeRS two-component system in Staphylococcus aureus is critical for regulation of many virulence genes, including hla, which encodes alpha-toxin. However, the impact of regulation of alpha-toxin by Sae on S. aureus pathogenesis has not been directly addressed. Here, we mutated the SaeR-binding sequences in the hla regulatory region and determined the contribution of this mutation to hla expression and pathogenesis in strain USA300 JE2. Western blot analyses revealed drastic reduction of alpha-toxin levels in the culture supernatants of SaeR-binding mutant in contrast to the marked alpha-toxin production in the wild type. The SaeR-binding mutation had no significant effect on alpha-toxin regulation by Agr, MgrA, and CcpA. In animal studies, we found that the SaeR-binding mutation did not contribute to USA300 JE2 pathogenesis using a rat infective endocarditis model. However, in a rat skin and soft tissue infection model, the abscesses on rats infected with the mutant were significantly smaller than the abscesses on those infected with the wild type but similar to the abscesses on those infected with a saeR mutant. These studies indicated that there is a direct effect of hla regulation by SaeR on pathogenesis but that the effect depends on the animal model used.
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PMID:Contribution of hla Regulation by SaeR to Staphylococcus aureus USA300 Pathogenesis. 3120 48


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