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Query: UMLS:C0243026 (sepsis)
 52,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Streptococcus agalactiae (group B streptococcus [GBS]) is a leading cause of neonatal pneumonia, sepsis, and meningitis. Early-onset GBS pneumonia is characterized by marked pulmonary epithelial and endothelial cell injury. Innate proinflammatory responses to GBS infection that may contribute to the respiratory pathology include the synthesis and release of cytokines, prostaglandins, and nitric oxide (NO). The hypothesis that NO is directly induced in lung epithelial cells by invading GBS or indirectly induced by cytokines released by GBS-infected mononuclear cells was tested. A549 transformed human respiratory epithelial cells were directly cultured with GBS, cocultured with GBS-infected human mononuclear cells or purified macrophages, or exposed to conditioned culture medium from human mononuclear cells infected by GBS. The culture medium of A549 cultures was assayed for NO secretion, and the cell lysates were tested for presence of inducible nitric oxide synthase (iNOS) mRNA by reverse transcriptase PCR (RT-PCR). GBS-treated A549 cells neither secreted detectable NO nor expressed iNOS mRNA. GBS interaction with human mononuclear cells, however, stimulated release of soluble factors that readily induced iNOS mRNA expression and NO secretion by A549 cells. Inflammatory mediator-induced nitric oxide (NO) production by alveolar epithelium may exceed that of other lung cell types such as macrophages, and induction during GBS infection may play a significant role in pulmonary defense or free-radical-mediated lung injury.
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PMID:Cytokine responses to group B streptococci induce nitric oxide production in respiratory epithelial cells. 1174 62

Group B streptococcus (GBS; Streptococcus agalactiae) is the most common cause of neonatal and obstetric sepsis and is an increasingly important cause of septicemia in elderly individuals and immunocompromised patients. Ongoing surveillance to monitor GBS serotype distribution will be needed to guide the development and use of GBS conjugate vaccines. We designed sequencing primers based on the previously published sequences of the capsular polysaccharide (cps) gene clusters to further define partial cps gene clusters for eight of the nine GBS serotypes (serotypes Ia to VII). Subsequently, we designed and evaluated primers to identify serotypes Ia, Ib, III, IV, V, and VI directly by PCR and all eight serotypes (serotypes Ia to VII) by sequence heterogeneity. A total of 206 clinical GBS isolates were used to compare our molecular serotype (MS) identification method with conventional serotyping (CS). All clinical isolates were assigned an MS, whereas 188 of 206 (91.3%) were assigned a serotype by use of antisera. A small number of isolates (serosubtypes III-3 and III-4) showed different serotype specificities between PCR and sequencing, but the PCR results correlated with those obtained by CS. The overall agreement between the MS identification method and CS for isolates for which results of both tests were available was 100% (188 of 188 isolates). The MS identification method is a specific and practical alternative to conventional GBS serotyping and will facilitate epidemiological studies.
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PMID:Serotype identification of group B streptococci by PCR and sequencing. 1177 19

Neonatal bacterial sepsis is often characterized by a fulminant clinical course and highly elevated plasma levels of proinflammatory cytokines. To evaluate in vitro activation of the neonatal immune system by specific infectious stimuli, cord blood cells from healthy neonates were examined for expression of tumor necrosis factor-alpha (TNF-alpha), IL-1beta, IL-6, and IL-8 in response to Streptococcus agalactiae (GBS), lipopolysaccharide (LPS), and lipoteichoic acid (LTA). Cytokine-expression was compared in mononuclear cells from cord and adult peripheral blood. TNF-alpha and IL-6 levels in the supernatant of cord blood cell cultures were significantly higher after stimulation with heat-killed GBS (10(7)/mL) than with LPS (2 microg/mL) or LTA (2 microg/mL) (TNF-alpha: 2215 versus 267.5 versus 40 pg/mL, p = 0.001; IL-6: 9667 versus 4909 versus 919 pg/mL, p = 0.006). mRNA expression of TNF-alpha, IL-1beta, IL-6, and IL-8 was equally pronounced after stimulation with either GBS, LPS, or LTA in cord or adult blood cells at various times. A MAb directed against the monocyte receptor molecule CD14 did not inhibit the release of cytokines in cord blood mononuclear cells after stimulation with GBS. In summary, activation of cord blood cells by infectious stimuli is comparable to the adult immune response in terms of expression of proinflammatory cytokines. GBS in particular proves to be a potent activator of the neonatal immune system when compared with LPS and LTA. CD14 seems not to be a crucial molecule for activation of cord blood cells by GBS.
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PMID:Cytokine expression of cord and adult blood mononuclear cells in response to Streptococcus agalactiae. 1186 34

Bacterial antigenic challenge presents a difficult fight for the neonatal immune system, and they have a smaller arsenal of weapons to fight bacterial infections than adults and older children. The baby's own systemic inflammatory response may have detrimental effects on several organs and longer lasting effects on the developing brain. Neurodevelopmental outcomes after maternal chorioamnionitis are worse than neonates without a contaminated intrauterine environment, regardless of gestation age and the baby's culture results. Successes with intrapartum antibiotic prophylaxis decreasing rates of GBS sepsis and maternal chorioamnionitis, have heartened care providers and parents. These results demonstrate the advances possible when specific diseases are made a national health priority, and good clinical trial work is applied to clinical practice.
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PMID:Neonatal sepsis: evaluation and management. 1212 92

Group B streptococcus (Streptococcus agalactiae) or GBS is the most common cause of neonatal sepsis and meningitis in the United States. One important risk factor for infants who acquire GBS is maternal colonization. Colonization rates have been estimated in various studies to be between 15% and 35% of pregnant women. Colonization rates for black women have also been shown to be higher than for non-blacks. Local data were collected and compared to those of other studies. Of the pregnant women in this study overall, 22.76% tested positive for GBS. Black women were colonized by GBS (35.71%) significantly more often than non-black women (19.84%; G = 8.9729, p < 0.00274). Generalized linear models were used to examine age and race. Both maternal age and the interaction of maternal race and age as predictors of infection were ruled out, leaving only race as a significant predictor of colonization.
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PMID:The incidence of group B streptococcus in the vaginal tracts of pregnant women in central Alabama. 1277 51

Streptococcus agalactiae (Group B Streptococcus: GBS) is the major causative agent of neonatal sepsis. Neonates at risk for GBS infections are empirically administered broad-spectrum antibiotics for at least 48 h pending blood culture results. A rapid assay to expedite detection of GBS would facilitate initiation of specific antibiotic therapy. Conversely, expeditious proof of absence of infection will avoid unnecessary antibiotic use. Using the LightCycler, we evaluated a hybridization probe polymerase chain reaction (PCR) assay to detect GBS-specific cfb gene target DNA sequence in blood specimens. Both sensitivity and specificity of the real-time PCR assay was 100%. The assay demonstrated 100% specificity when tested against 26 non-GBS bacteria. This method is capable of detecting as few as approximately 100 copies or 10 pg of GBS genomic DNA. This real-time PCR method is rapid, sensitive, and specific for the detection of GBS in neonatal blood samples and holds great promise in its utility in the diagnostic laboratory.
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PMID:Evaluation of a real-time fluorescent PCR assay for rapid detection of Group B Streptococci in neonatal blood. 1538 Feb 73

Streptococcus agalactiae (GBS) is a causative agent of sepsis and meningitis in newborns and diseases in pregnant women and nonpregnant adults. Various approaches, including both nongenetic and genetic techniques, are currently used for the study of epidemiology of GBS infections. In the present paper the different methods of molecular epidemiology of GBS infections are reviewed, and several novel approaches are introduced. The advantages and disadvantages of molecular methods are discussed and compared with traditional serotyping technique. The possible use of the molecular approaches for identification of different genetic lineages in GBS as well as for identification and control of the epidemiologically actual clones is discussed.
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PMID:Molecular epidemiology of group B streptococcal infections. 1553 3

In this study, we carried out a detailed structural and functional analysis of a Streptococcus agalactiae (GBS) two-component system which is orthologous to the CovS/CovR (CsrS/CsrR) regulatory system of Streptococcus pyogenes. In GBS, covR and covS are part of a seven gene operon transcribed from two promoters that are not regulated by CovR. A DeltacovSR mutant was found to display dramatic phenotypic changes such as increased haemolytic activity and reduced CAMP activity on blood agar. Adherence of the DeltacovSR mutant to epithelial cells was greatly increased and analysis by transmission electron microscopy revealed the presence at its surface of a fibrous extracellular matrix that might be involved in these intercellular interactions. However, the DeltacovSR mutant was unable to initiate growth in RPMI and its viability in human normal serum was greatly impaired. A major finding of this phenotypic analysis was that the CovS/CovR system is important for GBS virulence, as a 3 log increase of the LD(50) of the mutant strain was observed in the neonate rat sepsis model. The pleiotropic phenotype of the DeltacovSR mutant is in full agreement with the large number of genes controlled by CovS/CovR as seen by expression profiling analysis, many of which encode potentially secreted or cell surface-associated proteins: 76 genes are repressed whereas 63 were positively regulated. CovR was shown to bind directly to the regulatory regions of several of these genes and a consensus CovR recognition sequence was proposed using both DNase I footprinting and computational analyses.
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PMID:CovS/CovR of group B streptococcus: a two-component global regulatory system involved in virulence. 1555 66

Streptococcus agalactiae (group B Streptococcus, GBS) is an important cause of sepsis and meningitis in neonates, and excessive production of the inflammatory mediators tumor necrosis factor (TNF) and nitric oxide (NO) causes tissue injury during severe infections. We hypothesized that exposure of GBS to different antimicrobial agents would affect the magnitude of the macrophage inflammatory response to this organism. We stimulated RAW 264.7 murine macrophages with a type-Ia GBS isolate in the presence of ampicillin, cefotaxime, rifampin, clindamycin, or gentamicin, singly or in combination. We found that GBS exposed to rifampin or clindamycin (versus beta-lactam antibiotics) stimulated less TNF secretion and inducible nitric oxide synthase (iNOS) protein accumulation in RAW 264.7 cells. Furthermore, GBS exposed to combinations of antibiotics that included a protein synthesis inhibitor stimulated less macrophage TNF and iNOS production than did organisms exposed to beta-lactam antibiotics singly or in combination. We conclude that exposure of GBS to rifampin or clindamycin leads to a less pronounced macrophage inflammatory mediator response than does exposure of the organism to cell wall-active antibiotics.
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PMID:Group B streptococci exposed to rifampin or clindamycin (versus ampicillin or cefotaxime) stimulate reduced production of inflammatory mediators by murine macrophages. 1563 47

Streptococcus agalactiae (group B streptococcus [GBS]) is the leading cause of neonatal pneumonia, sepsis, and meningitis. An in silico genome analysis indicated that GBS strain NEM316 encodes 35 proteins containing an LPXTG motif which are thought to be covalently linked to the peptidoglycan by an enzyme called sortase. The role of these cell wall-anchored proteins in GBS pathogenesis was evaluated on a global level by inactivating the srtA gene. This gene encodes the major sortase SrtA that anchors most of the LPXTG-containing proteins. We chose the C5a peptidase (ScpB) and Alp2, an abundant immunogenic protein, as prototypical LPXTG-containing proteins. As expected, the SrtA knockout mutant was unable to anchor the C5a peptidase (ScpB) and Alp2 to the cell wall. Complementation with plasmid-borne srtA inserted into the chromosome restored the correct surface localization of both ScpB and Alp2. Interestingly, the SrtA mutant was impaired for binding to the major extracellular matrix components fibronectin and fibrinogen and displayed a significant reduction in adherence to human (A549, HeLa, and Caco-2) and murine (L2) epithelial cells compared to the parental wild-type strain. Surprisingly, the inactivation of srtA had no effect on the virulence of the type III strain of GBS in a neonatal rat model (measured by the 50% lethal dose and lung colonization) but strongly impaired the capacity of the strain to colonize the intestines of gnotobiotic mice in a competition assay. These results demonstrate that LPXTG-containing proteins are involved in cell adhesion and GBS persistence in vivo.
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PMID:The SrtA Sortase of Streptococcus agalactiae is required for cell wall anchoring of proteins containing the LPXTG motif, for adhesion to epithelial cells, and for colonization of the mouse intestine. 1590 60


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