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)

The emergence of clinical isolates of methicillin-resistant Staphylococcus aureus with reduced susceptibility to vancomycin has prompted a search for new and novel therapeutic agents active against S. aureus. Lysostaphin, a peptidase produced by Staphylococcus simulans, specifically cleaves the glycine-glycine bonds unique to the interpeptide cross-bridge of the S. aureus cell wall. The effectiveness of various regimens of dosing with intravenous lysostaphin was compared to that of vancomycin in the rabbit model of aortic valve endocarditis caused by a clinical methicillin-resistant S. aureus isolate. All animals were treated for a total of 3 days. The most active regimen, lysostaphin given three times daily, produced sterile vegetations in 10 of 11 treated rabbits, with a mean reduction in vegetation bacterial counts of 8.5 log10 CFU/g compared to the counts in the untreated controls. In contrast, vancomycin given twice daily sterilized no vegetations and reduced vegetation bacterial counts by only 4.8 log10 CFU/g. Lysostaphin given once daily was less effective, reducing mean vegetation bacterial counts by only 3.6 log10 CFU/g, but the combination of lysostaphin once daily and vancomycin twice daily reduced the mean vegetation bacterial density by 7.5 log10 CFU/g, a result that was significantly better than that for either regimen alone (P < 0.05). Lysostaphin was well tolerated by the rabbits, with no evidence of immunological reactions following up to 9 weeks of intravenous administration. We conclude that lysostaphin given alone or in combination with vancomycin is more effective in the treatment of experimental methicillin-resistant S. aureus aortic valve endocarditis than vancomycin alone.
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PMID:Lysostaphin treatment of experimental methicillin-resistant Staphylococcus aureus aortic valve endocarditis. 962 75

The synthesis of cell-associated and secreted proteins by Streptococcus gordonii FSS2, an infective endocarditis (IE) isolate, was influenced by both environmental pH and carbon source. Controlling the pH at 7.5 in stirred batch cultures showed that cell-associated and secreted protein concentrations were increased during late exponential and stationary phase by 68% and 125%, respectively, compared with similar cultures without pH control. The expression of five glycosidase and eight peptidase activities were examined using fluorogen-labelled synthetic substrates. Enzyme activities were significantly down-regulated during exponential growth, increasing during stationary phase (P<0.01) whether the culture pH was controlled at pH 7.5 or allowed to fall naturally to pH 4.4. Culture-supernatant activities were significantly increased (P<0.05) when the pH was maintained at 6.0 or 7.5, indicating modulation of enzyme activity by pH. Growth under nitrogen-limitation/glucose-excess conditions resulted in a significant repression of cell-associated glycosidase activities (P<0.01), whilst in the supernatant, activities were generally reduced. The expression of peptidase activities in the culture supernatant did not significantly change. The results suggest a possible role for catabolite repression by glucose in regulating enzyme expression. When S. gordonii FSS2 was cultured with 50% (v/v) added heat-inactivated foetal bovine serum, several cell-associated enzyme activities increased initially but were then reduced as the culture time was extended to 116 h. Culture-supernatant enzyme activities (N-acetyl-beta-D-glucosaminidase, N-acetyl-beta-D-galactosaminidase, thrombin, Hageman factor, collagenase and chymotrypsin), however, were significantly increased (P<0.01) over the same time period. The findings indicated that most of the important glycosidases synthesized by S. gordonii FSS2 were down-regulated by acid growth conditions and may also be subject to catabolite repression by glucose but conversely may be up-regulated by growth in serum. These results may have implications for streptococcal growth in an IE vegetation and in the mouth between meals or during sleep.
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PMID:Environmental regulation of glycosidase and peptidase production by Streptococcus gordonii FSS2. 1093 96

The present study shows that active, self-splicing group II intron GBSi1 is located downstream of the C5a-peptidase gene, scpB, in some group B streptococcus (GBS) isolates that lack insertion sequence IS1548. IS1548 was previously reported to be often present at the scpB locus in GBS isolated in association with endocarditis. Since none of 67 GBS isolates examined, 40 of which were of serotype III, harbored both IS1548 and GBSi1, these two elements are suggested to be markers for different genetic lineages in GBS serotype III. The DNA region downstream of scpB in GBS isolates harboring either GBSi1, IS1548, or none of these mobile elements was found to encode the laminin binding protein, Lmb, which shows sequence similarities to a family of streptococcal adhesins. IS1548 is inserted 9 bp upstream of the putative promoter for lmb, while the insertion site for GBSi1 is located 88 bp further upstream. Sequences highly similar to GBSi1 exist also in Streptococcus pneumoniae. An inverted repeat sequence, with features typical of transcription terminators, was identified immediately upstream of the insertion site for the group II intron both in the GBS and S. pneumoniae sequences. This motif is suggested to constitute a target for the GBS intron as well as for rather closely related introns in Bacillus halodurans, Pseudomonas alcaligenes, and Pseudomonas putida. When transcripts containing the GBSi1 intron were incubated at high concentrations of ammonium and magnesium, a major product with the expected length and sequence for the ligated exons was generated. Unlike, however, all members of group II investigated so far, the excised intron was in linear, rather than in a branched (lariat), form.
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PMID:Mutually exclusive distribution of IS1548 and GBSi1, an active group II intron identified in human isolates of group B streptococci. 1127 16