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

The importance of viridans streptococci as agents of serious extra-oral diseases, including endocarditis, is now recognized. We have tested the hypothesis that the ability to utilize sialic acid as a nutrient source may play a role in the proliferation of these organisms. The type strains of the 15 presently recognized species of viridans streptococci and two clinical isolates-S. oralis (AR3), isolated from a patient with infective endocarditis, and S. intermedius (UNS35), a brain abscess isolate-were studied for their ability to utilize sialic acid. Only S. oralis, S. sanguis, S. gordonii, S. mitis ("oralis group") S. intermedius, S. anginosus, S. constellatus ("milleri group"), and S. defectivus ("nutritionally variant group") were able to use sialic acid (N-acetylneuraminic acid) efficiently as a sole carbon source. Formate, acetate, and ethanol were produced as the major metabolic end-products of sialic acid metabolism, while corresponding glucose-grown cultures produced lactate as the major metabolic end-product. Utilization of sialic acid was independent of the production of sialidase. Cell-free extracts of sialic acid-grown cultures expressed elevated levels of N-acetylneuraminate pyruvate-lyase (NPL; the first enzyme in the intracellular catabolism of sialic acid) and N-acetylglucosamine-6-phosphate (GlcNAc-6-P) deacetylase and glucosamine-6-phosphate (GlcN-6-P) deaminase (enzymes involved in the intracellular catabolism of N-acetylglucosamine). These activities were repressed by growth in the presence of glucose. The intracellular fate of sialic acid, after cleavage by NPL into N-acetylmannosamine (ManNAc) and pyruvate, is uncertain, but the elevated levels of GlcNAc-6-P deacetylase and GlcN-6-P deaminase in sialic acid-grown cells suggest that phosphorylation and isomerization are possible steps in the metabolism of ManNAc to generate an intermediate common to the pathway of N-acetylglucosamine metabolism. The species of viridans streptococci that have the ability to utilize sialic acid are those most commonly associated with extra-oral diseases, and this ability is likely to play a role in the persistence and survival of these infecting organisms in vivo.
...
PMID:Utilization of sialic acid by viridans streptococci. 890 24

Streptococcus oralis has emerged as one of the most important organisms of the viridans streptococcus group in terms of infections and is recognised as an agent of infective endocarditis and, in immunocompromised patients, septicaemia. The mechanisms by which this organism proliferates in vivo are unknown. However, host-derived sialic acids -- including N-acetylneuraminic acid (NeuNAc) which is present in serum and cell-associated glycoproteins -- are a potential source of fermentable carbohydrate for bacterial proliferation, especially for sialidase-producing bacteria, including S. oralis. To further elucidate the role of NeuNAc in supporting growth, this study determined the ability of S. oralis strain AR3 (isolated from a patient with infective endocarditis) to transport NeuNAc and characterised the transport system. The transport of [14C]-labelled NeuNAc into S. oralis was monitored and this transport system was induced by growth of the bacteria in the presence of the N-acetylated sugars NeuNAc, N-acetylglucosamine and N-acetylmannosamine. The transport system followed typical Michaelis-Menten kinetics, with a Km of 21.0 microM and a Vmax of 2.65 nmoles of NeuNAc transported/min/mg of dry cell mass. NeuNAc transport was inhibited by the presence of exogenous N-glycolylneuraminic acid, a related sialic acid. Chlorhexidine, NaF and 2,4-dinitrophenol were potent inhibitors of the transport system, suggesting that the uptake of NeuNAc occurs via a proton motive force-dependent permease system. This is the first report of the mechanism by which NeuNAc transport occurs in pathogenic streptococci. This transport process may have relevance to the acquisition of a source of fermentable carbohydrate and thus bacterial proliferation in vivo.
...
PMID:N-acetylneuraminic acid transport by Streptococcus oralis strain AR3. 1050 80

Nowadays, Enterococcus faecium is one of the leading nosocomial pathogens worldwide. Strains causing clinical infections or hospital outbreaks are enriched in the enterococcal surface protein (Esp) encoding ICEEfm1 mobile genetic element. Previous studies showed that Esp is involved in biofilm formation, endocarditis and urinary tract infections. In this study, we characterized the role of the putative AraC type of regulator (locus tag EfmE1162_2351), which we renamed ebrB and which is, based on the currently available whole genome sequences, always located upstream of the esp gene, and studied its role in Esp surface exposure during growth. A markerless deletion mutant of ebrB resulted in reduced esp expression and complete abolishment of Esp surface exposure, while Esp cell-surface exposure was restored when this mutant was complemented with an intact copy of ebrB. This demonstrates a role for EbrB in esp expression. However, during growth, ebrB expression levels did not change over time, while an increase in esp expression at both RNA and protein level was observed during mid-log and late-log phase. These results indicate the existence of a secondary regulation system for esp, which might be an unknown quorum sensing system as the enhanced esp expression seems to be cell density dependent. Furthermore, we determined that esp is part of an operon of at least 3 genes putatively involved in biofilm formation. A semi-static biofilm model revealed reduced biofilm formation for the EbrB deficient mutant, while dynamics of biofilm formation using a flow cell system revealed delayed biofilm formation in the ebrB mutant. In a mouse intestinal colonization model the ebrB mutant was less able to colonize the gut compared to wild-type strain, especially in the small intestine. These data indicate that EbrB positively regulates the esp operon and is implicated in biofilm formation and intestinal colonization.
...
PMID:The Enterococcus faecium enterococcal biofilm regulator, EbrB, regulates the esp operon and is implicated in biofilm formation and intestinal colonization. 2374 84

Streptococcus sanguinis is a pioneer species of teeth and a common opportunistic pathogen of infective endocarditis. In this study, we identified a two-component system, S. sanguinis SptRS (SptRS Ss ), affecting S. sanguinis survival in saliva and biofilm formation. Isogenic mutants of sptRSs (SKsptR) and sptSSs (SKsptS) showed reduced cell counts in ex vivo assays of viability in saliva compared to those of parent strain SK36 and complemented mutants. Reduced counts of the mutants in saliva were associated with reduced growth rates in nutrient-poor medium (RPMI) and increased susceptibility to the deposition of C3b and the membrane attach complex (MAC) of the complement system, a defense component of saliva and serum. Conversely, sptRSs and sptSSs mutants showed increased biofilm formation associated with higher levels of production of H2O2 and extracellular DNA. Reverse transcription-quantitative PCR (RT-qPCR) comparisons of strains indicated a global role of SptRS Ss in repressing genes for H2O2 production (2.5- to 15-fold upregulation of spxB, spxR, vicR, tpk, and ackA in sptRSs and sptSSs mutants), biofilm formation, and/or evasion of host immunity (2.1- to 11.4-fold upregulation of srtA, pcsB, cwdP, iga, and nt5e). Compatible with the homology of SptR Ss with AraC-type regulators, duplicate to multiple conserved repeats were identified in 1,000-bp regulatory regions of downstream genes, suggesting that SptR Ss regulates transcription by DNA looping. Significant transcriptional changes in the regulatory genes vicR, spxR, comE, comX, and mecA in the sptRSs and sptSSs mutants further indicated that SptRS Ss is part of a regulatory network that coordinates cell wall homeostasis, H2O2 production, and competence. This study reveals that SptRS Ss is involved in the regulation of crucial functions for S. sanguinis persistence in the oral cavity.
...
PMID:Novel Two-Component System of Streptococcus sanguinis Affecting Functions Associated with Viability in Saliva and Biofilm Formation. 2933 59