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)

Amoxicillin is one of the most frequently recommended antibiotics for prophylaxis of infective endocarditis in dental/oral procedures. In this study, the postantibiotic effect (PAE), postantibiotic sub-MIC (PASME) and sub-MIC effect (SME) of amoxicillin on oral streptococci, Streptococcus gordonii and Streptococcus sanguis, which are two of the major etiological agents in infective endocarditis, were investigated. The PAE was induced by 10 x MIC of amoxicillin for 2 h and the antibiotic was eliminated by washing. The PASMEs were studied by addition of 0.1, 0.2 and 0.3 x MICs during the postantibiotic phase of the bacteria, and the SMEs were studied by exposing bacteria to amoxicillin at the sub-MICs only. The PAE of amoxicillin was 2.0 h with S. gordonii DL1 and 0.7 h with S. sanguis MPC1. The PASME and SME of amoxicillin were observed both for S. gordonii DL1 and for S. sanguis MPC1. However, the durations of effects for S. sanguis MPC1 were shorter than those for S. gordonii DL1. The PASME values for both strains increased as the concentration of amoxicillin increased. The PASME values for both strains were substantially longer than the SME values. The present study illustrates the existence of PAE, PASME and SME for amoxicillin against S. gordonii and S. sanguis, thereby extending the pharmacodynamic advantages of amoxicillin for these bacteria in the prophylaxis procedures of infective endocarditis.
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PMID:Postantibiotic effects and postantibiotic sub-MIC effects of amoxicillin on Streptococcus gordonii and Streptococcus sanguis. 1112 56

Thrombin-induced platelet microbicidal proteins (tPMP) are alpha-granule-derived cationic antimicrobial proteins released from platelets by stimulation with thrombin. tPMP has potent microbicidal activities against a broad spectrum of common microbial pathogens in infective endocarditis. We studied in vitro interactions of tPMP with penicillin against oral streptococci, Streptococcus rattus BHT (a tPMP-susceptible organism) and Streptococcus gordonii DL1 (a tPMP-insusceptible organism). tPMP was prepared by stimulating rabbit platelets with thrombin. tPMP plus penicillin showed a synergistic bactericidal effect on both S. rattus BHT and S. gordonii DL1, in contrast to either agent alone. Sequential exposure of both S. rattus BHT and S. gordonii DL1 to tPMP followed by exposure to penicillin at 10x the MICs resulted in a significant extension of the postantibiotic-effect duration compared with antibiotic exposure alone. The combined data indicate that tPMP exerts cooperative bactericidal and growth-inhibiting effect in concert with penicillin.
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PMID:Penicillin-induced killing and postantibiotic effect in oral streptococci are enhanced by platelet microbicidal proteins. 1512 Jul 23

Bacterial recognition of host sialic acid-containing receptors plays an important role in microbial colonization of the human oral cavity. The sialic acid-binding adhesin of Streptococcus gordonii DL1 was previously associated with the hsa gene encoding a 203-kDa protein. The predicted protein sequence consists of an N-terminal nonrepetitive region (NR1), including a signal sequence, a relatively short serine-rich region (SR1), a second nonrepetitive region (NR2), a long serine-rich region (SR2) containing 113 dodecapeptide repeats, and a C-terminal cell wall anchoring domain. In the present study, the contributions of SR1, NR2, and SR2 to Hsa-mediated adhesion were assessed by genetic complementation. Adhesion of an hsa chromosomal deletion mutant to sialic acid-containing receptors was restored by plasmids containing hsa constructs encoding Hsa that lacked either the N- or C-terminal portion of SR2. In contrast, hsa constructs that lacked the coding sequences for SR1, NR2, or the entire SR2 region failed to restore adhesion. Surface expression of recombinant Hsa was not affected by removal of SR1, NR2, or a portion of SR2 but was greatly reduced by complete removal of SR2. Wheat germ agglutinin, a probe for Hsa-specific glycosylation, reacted with recombinant Hsa lacking SR1, NR2, or SR2 but not with recombinant Hsa lacking both SR1 and SR2. Significantly, the aggregation of human platelets by S. gordonii DL1, an interaction implicated in the pathogenesis of infective endocarditis, required the expression of hsa. Moreover, neuraminidase treatment of the platelets eliminated this interaction, further supporting the hypothesis that Hsa plays an essential role in the bacterium-platelet interaction.
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PMID:Functional analysis of the Streptococcus gordonii DL1 sialic acid-binding adhesin and its essential role in bacterial binding to platelets. 1521 30

Aggregation of human platelets by Streptococcus gordonii DL1, an interaction implicated in the pathogenesis of infective endocarditis, requires the expression of hsa, the gene encoding the sialic acid-binding adhesin (Hsa) of this organism. To identify the sialoglycoproteins on the platelet surface as the receptors for Hsa, intrinsic membrane proteins were assessed by bacterial overlay assay. S. gordonii DL1 adhered to 130-140-kDa proteins, a reaction that was abolished by neuraminidase treatment of immobilized platelet surface proteins. These sialoglycoproteins were identified as platelet glycoprotein Ib alpha (GPIbalpha ) and glycoprotein IIb (GPIIb) by immunoprecipitation with specific monoclonal antibody against each glycoprotein.
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PMID:Identification of platelet receptors for the Streptococcus gordonii DL1 sialic acid-binding adhesin. 1611 9

An insertional mutation in hsa, the gene encoding the sialic acid-binding adhesin of Streptococcus gordonii DL1, resulted in a significant reduction of the infection rate of the organism and an inflammatory reaction in the rat aortic valve with experimental endocarditis, suggesting that the adhesin contributes to the infectivity of the organism for heart valves.
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PMID:Contribution of sialic acid-binding adhesin to pathogenesis of experimental endocarditis caused by Streptococcus gordonii DL1. 1636 32

Significant differences in virulence among seven representative Streptococcus gordonii strains were observed by using the rat model of infective endocarditis. Five strains, including S. gordonii DL1, caused severe disease, while the other two strains, including S. gordonii SK12, caused minimal or no disease. The differences in virulence were evident from the visible presence of streptococci in the vegetations present on the aortic valves of catheterized rats that were challenged with individual strains and also from the much greater recovery of rifampin-resistant S. gordonii DLl than of streptomycin-resistant S. gordonii SK12 from the hearts of animals coinfected with both organisms. Each S. gordonii strain aggregated with human platelets and bound to polymorphonuclear leukocytes (PMNs), as shown by the stimulation of PMN superoxide anion production. These interactions were reduced or abolished by pretreatment of the platelets or PMNs with sialidase, indicating that there was bacterial recognition of host sialic acid-containing receptors. Adhesin-mediated binding of each S. gordonii strain to PMNs also triggered phagocytosis. However, the subsequent PMN-dependent killing differed significantly for the seven strains. The five virulent strains included three strains that were not killed and two strains whose numbers were reduced by approximately 50%. In contrast, the level of killing of each avirulent strain under the same conditions was significantly greater and approached 90% of the bacteria added. Parallel studies performed with rat PMNs revealed comparable differences in the resistance or susceptibility of representative virulent and avirulent strains. Thus, the ability of S. gordonii to survive in PMNs following adhesin-mediated phagocytosis may be an important virulence determinant of infective endocarditis.
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PMID:Resistance of Streptococcus gordonii to polymorphonuclear leukocyte killing is a potential virulence determinant of infective endocarditis. 1671 42

Streptococcus gordonii colonization of damaged heart surfaces in infective endocarditis is dependent upon the recognition of host receptors by specific bacterial surface proteins. However, despite several attempts to identify the mechanisms involved in this interaction, the nature of the bacterial proteins required remains poorly understood. This study provides clear evidence that several S. gordonii surface proteins participate in the interaction with platelets to support platelet adhesion and induce platelet aggregation. S. gordonii strains were found to support strong (DL1-Challis, SK12, SK184, and Blackburn) or moderate (UB1545 delta hsa and CH1-Challis) adhesion or failed to support platelet adhesion (M5, M99, and Channon). In addition, under flow conditions, platelets rolled and subsequently adhered to immobilized S. gordonii at low shear (50 s(-1)) in an Hsa-dependent manner but did not interact with S. gordonii DL1 at any shear rate of >50 s(-1). S. gordonii strains either induced (DL1-Challis, SK12, SK184, UB1545 delta hsa, and M99) or failed to induce (M5, CH1-Challis, Channon, and Blackburn) platelet aggregation. Using a proteomic approach to identify differential cell wall protein expression between aggregating (DL1) and nonaggregating (Blackburn) strains, we identified antigen I/antigen II family proteins SspA and SspB. The overexpression of SspA or SspB in platelet-nonreactive Lactococcus lactis induced GPIIb/GPIIIa-dependent platelet aggregation similar to that seen with S. gordonii DL1. However, they failed to support platelet adhesion. Thus, S. gordonii has distinct mechanisms for supporting platelet adhesion and inducing platelet aggregation. Differential protein expression between strains may be important for the pathogenesis of invasive diseases such as infective endocarditis.
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PMID:Role of Streptococcus gordonii surface proteins SspA/SspB and Hsa in platelet function. 1789 26

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

Infective endocarditis is frequently attributed to oral streptococci. The mechanisms of pathogenesis, however, are not well understood, although interaction between streptococci and phagocytes are thought to be very important. A highly expressed surface component of Streptococcus gordonii, Hsa, which has sialic acid-binding activity, contributes to infective endocarditis in vivo. In the present study, we found that S. gordonii DL1 binds to HL-60 cells differentiated into monocytes, granulocytes, and macrophages. Using a glutathione S-transferase (GST) fusion to the NR2 domain, which is the sialic acid-binding region of Hsa, we confirmed that the Hsa NR2 domain also binds to differentiated HL-60 cells. To identify which sialoglycoproteins on the surface of differentiated HL-60 cells are receptors for Hsa, intrinsic membrane proteins were assessed by bacterial overlay and far-Western blotting. S. gordonii DL1 adhered to 100- to 150-kDa proteins, a reaction that was abolished by neuraminidase treatment. These sialoglycoproteins were identified as CD11b, CD43, and CD50 by GST pull-down assay and immunoprecipitation with each specific monoclonal antibody. These data suggest that S. gordonii DL1 Hsa specifically binds to three glycoproteins as receptors and that this interaction may be the initial bacterial binding step in infective endocarditis by oral streptococci.
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PMID:Binding of the Streptococcus gordonii DL1 surface protein Hsa to the host cell membrane glycoproteins CD11b, CD43, and CD50. 1867 68

Surface adhesion plays an essential part in the survival of the commensal organism Streptococcus gordonii in the oral cavity as well as during opportunistic infections such as endocarditis. At least two types of cell surface protein involved in adhesion are found on the surface of Gram-positive bacteria: those anchored via an LPXTG motif by the enzyme sortase A (SrtA) and those associated with the cell surface by, as yet, unknown mechanisms. In srtA(-) mutants, LPXTG-containing proteins have been shown to be released rather than cross-linked to the cell wall. We have therefore used 2D gel electrophoresis of released proteins from an srtA(-) mutant as well as the wild-type strain, followed by peptide identification by MS, to identify a set of novel proteins predicted to be present on the surface of S. gordonii DL1. This includes two large LPXTG-linked proteins (SGO_0707 and SGO_1487), which both contain tandemly repeated sequences similar to those present in known fibrillar adhesins. A 5'-nucleotidase and a protein with a putative collagen-binding domain, both containing LPXTG motifs, were also identified. Anchorless proteins with known chaperone, stress response and elongation factor functions, apparently responsible for bacterial binding to keratinocytes and saliva-coated surfaces in the absence of the LPXTG-linked adhesins, were also associated with the cell surface. These data reveal a range of proteins to be present on the S. gordonii DL1 cell surface, the expression of which plays an important role in adhesion to epithelia and which represent likely candidates for novel virulence factors in S. gordonii.
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PMID:Identification of novel LPXTG-linked surface proteins from Streptococcus gordonii. 1938 83


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