Adaptive response of neonatal sepsis-derived Group B Streptococcus to bilirubin.
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ABSTRACT:
SUBMITTER: Hansen R
PROVIDER: S-EPMC5915570 | biostudies-literature | 2018 Apr
REPOSITORIES: biostudies-literature
Publications
Adaptive response of neonatal sepsis-derived Group B Streptococcus to bilirubin.
Hansen Richard R Gibson Sophie S De Paiva Alves Eduardo E Goddard Mark M MacLaren Andrew A Karcher Anne Marie AM Berry Susan S Collie-Duguid Elaina S R ESR El-Omar Emad E Munro Mike M Hold Georgina L GL
Scientific reports 20180424 1
Hyperbilirubinemia is so common in newborns as to be termed physiological. The most common bacteria involved in early-onset neonatal sepsis are Streptococcus agalactiae, commonly called Group B Streptococcus (GBS). Whilst previous studies show bilirubin has antioxidant properties and is beneficial in endotoxic shock, little thought has been given to whether bilirubin might have antibacterial properties. In this study, we performed a transcriptomic and proteomic assessment of GBS cultured in the ...[more]
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Project description:BackgroundGroup B Streptococcus (GBS) causes invasive infections in neonates and has been implicated as a cause of prelabour rupture of membranes, preterm delivery and stillbirths. The success of phase II trials of polyvalent polysaccharide GBS vaccines indicates that these infections are potentially preventable. Nigeria is the most populous country in Africa with one of the highest birth rates, one of the highest neonatal sepsis incidence rates and one of the highest mortality rates in the world. Therefore, before the possible introduction of preventive strategies such as intrapartum antibiotic prophylaxis or GBS vaccine into Nigeria, it is vital that there is accurate data on the aetiology of neonatal sepsis and on the incidence of GBS neonatal sepsis in particular. The objective of this study was to determine the incidence and aetiology of neonatal sepsis in Nigeria with a focus on GBS sepsis and also to assess the potential impact of a GBS vaccine.MethodsA literature search was conducted on the databases of African journals online, PubMed and Google Scholar for works conducted between 1987 to 2017. Case reports, reviews, and studies not stating specific culture methods or specific bacteria isolated were excluded. Data extracted included; incidence of neonatal sepsis, method of blood culture, blood volume, sample size, bacterial agents isolated and history of antibiotic use. PRISMA guidelines were followed and modified Down's and Black criteria used to evaluate the quality of studies.ResultsA total of 5,114 studies were reviewed for neonatal sepsis out of which 24 consisting of a total of 2,280 cases were selected for final review. Nine studies met criteria for assessment of hospital based incidence of neonatal sepsis representing 31,305 hospital births. The incidence of neonatal sepsis was 18.2/1000 livebirths with range from 7-55/1000 livebirths while the GBS incidence was 0.06/1000 livebirths with range from 0-2/1000 live births. We discovered various limitations such as identification techniques that could result in underestimation of the true incidence of GBS sepsis. Pathogens such as Klebsiella pneumoniae and Staphylococcus aureus were more commonly isolated than GBS.Implications of key findingsThe hospital based incidence of neonatal sepsis was high at 18.2/1000 live births while that due to GBS was 0.06/1000 live births. The burden of neonatal sepsis, including that attributable to GBS is substantial and could be reduced by preventive strategies such as intrapartum antibiotic prophylaxis or GBS vaccine. There is however very sparse meaningful data currently. Well planned prospective studies with larger sample sizes, more advanced isolation and identification techniques and those following up invasive disease cases for possible short and long term sequelae are needed-not only prior to possible introduction of the vaccine to determine the baseline epidemiology, but also thereafter to monitor its impact on the population. Strategies need to be developed to also reduce the morbidity and mortality attributable to other bacteria that have an incidence even greater than that of GBS.
| S-EPMC6049915 | biostudies-literature
Project description:To enhance understanding of how Streptococcus agalactiae (group B streptococcus, GBS) adapts during invasive infection, we performed a whole-genome transcriptome analysis after incubation with whole human blood. Global changes occurred in the GBS transcriptome rapidly in response to blood contact following shift from growth in a rich laboratory medium. Most (83%) of the significantly altered transcripts were down-regulated after 30 minutes of incubation in blood, and all functional categories of genes were abundantly represented. We observed complex dynamic changes in the expression of transcriptional regulators and stress response genes that allow GBS to rapidly adapt to blood. The transcripts of relatively few proven virulence genes were up-regulated during the first 90 minutes. However, a key discovery was that genes encoding proteins involved in interaction with the host coagulation/fibrinolysis system and bacterial-host interactions were rapidly up-regulated. Extensive transcript changes also occurred for genes involved in carbohydrate metabolism, including multi-functional proteins and regulators putatively involved in pathogenesis. Finally, we discovered that an incubation temperature closer to that occurring in patients with severe infection and high fever (40 degrees C) induced additional differences in the GBS transcriptome relative to normal body temperature (37 degrees C). Taken together, the data provide extensive new information about transcriptional adaptation of GBS exposed to human blood, a crucial step during GBS pathogenesis in invasive diseases, and identify many new leads for molecular pathogenesis research.
| S-EPMC2519835 | biostudies-literature
Project description:Although the contribution of carbohydrate catabolism to bacterial colonization and infection is well recognized, the transcriptional changes during these processes are still unknown. In this study, we have performed comparative global gene expression analysis of GBS in sugar-free versus high glucose milieu. The analysis revealed a differential expression of genes involved in metabolism, transport and host-pathogen interaction. Many of them appeared to be among the genes previously reported to be controlled by the CovRS two-component system. Indeed, the transcription profile of a ?covRS strain grown in high-glucose conditions was profoundly affected. In particular, of the total genes described to be regulated by glucose, ?27% were under CovRS control with a functional role in protein synthesis, transport, energy metabolism and regulation. Among the CovRS dependent genes, we found bibA, a recently characterized adhesin involved in bacterial serum resistance and here reported to be down-regulated by glucose. ChIP analysis revealed that in the presence of glucose, CovR binds bibA promoter in vivo, suggesting that CovR may act as a negative regulator or a repressor. We also demonstrated that, as for other target promoters, chemical phosphorylation of CovR in aspartic acid increases its affinity for the bibA promoter region. The data reported in this study contribute to the understanding of the molecular mechanisms modulating the adaptation of GBS to glucose.
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Project description:Group B Streptococcus (GBS) is the major cause of human neonatal infections. A single clone, designated CC17-GBS, accounts for more than 80% of meningitis cases, the most severe form of the infection. However, the events allowing blood-borne GBS to penetrate the brain remain largely elusive. In this study, we identified the host transmembrane receptors α5β1 and αvβ3 integrins as the ligands of Srr2, a major CC17-GBS-specific adhesin. Two motifs located in the binding region of Srr2 were responsible for the interaction between CC17-GBS and these integrins. We demonstrated in a blood-brain-barrier cellular model that both integrins contributed to the adhesion and internalization of CC17-GBS. Strikingly, both integrins were overexpressed during the postnatal period in the brain vessels of the blood-brain barrier and blood-cerebrospinal fluid barrier and contributed to juvenile susceptibility to CC17 meningitis. Finally, blocking these integrins decreased the ability of CC17-GBS to cross into the CNS of juvenile mice in an in vivo model of meningitis. Our study demonstrated that CC17-GBS exploits integrins in order to cross the brain vessels, leading to meningitis. Importantly, it provides host molecular insights into neonate's susceptibility to CC17-GBS meningitis, thereby opening new perspectives for therapeutic and prevention strategies of GBS-elicited meningitis.
| S-EPMC7919713 | biostudies-literature
Project description:Neonatal sepsis continues to be a major cause of morbidity and mortality in India. To aid the diagnosis several direct and indirect methods are available. Sepsis screen has resulted in decrease in indiscriminate use of antibiotics. C-reactive protein can be easily estimated and is a useful indicator for favourable outcome or complication. The bacterial flora causing sepsis has changed over the years. Antimicrobial chemotherapy should be based on the prevalent organisms in the neonatal ICU. Outcome can be improved by judicious use of newer antibiotics and exchange transfusion when indicated.
| S-EPMC5531238 | biostudies-other
Project description:Purpose of Review:Neonatal sepsis is a diagnosis made in infants less than 28 days of life and consists of a clinical syndrome that may include systemic signs of infection, circulatory shock, and multisystem organ failure. Recent Findings:Commonly involved bacteria include Staphylococcus aureus and Escherichia coli. Risk factors include central venous catheter use and prolonged hospitalization. Neonates are at significant risk of delayed recognition of sepsis until more ominous clinical findings and vital sign abnormalities develop. Blood culture remains the gold standard for diagnosis. Summary:Neonatal sepsis remains an important diagnosis requiring a high index of suspicion. Immediate treatment with antibiotics is imperative.
| S-EPMC7100521 | biostudies-literature
Project description:The aims of this study were to describe the adherence to CDC guidelines for intrapartum antibiotic prophylaxis (IAP) and to identify possible factors influencing noncompliance with guidelines. We conducted a retrospective study in Italy. Our cohort included women in whom antenatal Group B Streptococcus (GBS) screening was not performed, was performed, but results were not available at the time of labor or delivery and women who were positive for GBS colonization. The indications for complete execution of IAP according to revised CDC guidelines was evaluated. It was considered adequate when performed with a recommended antibiotic at least four hours prior to delivery. The cohort included 902 women. Among those who had performed rectal and vaginal swabs (or recto-vaginal swabs), results were available in 86.9% of vaginal swabs and in 87.1% of rectal swabs and GBS was detected in 59.8% of vaginal swabs and in 71% of rectal swabs. 49.2% women had indication for GBS prophylaxis. Among these, 91.1% received an antibiotic during labor. Totally appropriate IAP was performed in 36.3% deliveries, an inappropriate antibiotic was administered in 10.4% women, the remaining 45.3% women received partially appropriate IAP; of these, 15.5% had received antibiotics through an inappropriate route of administration, 18.2% an inappropriate dosage regimen. Overall, 27.5% women received intrapartum ampicillin with inappropriate timing. Multivariate analysis showed that totally appropriate prophylaxis was significantly more likely in women who had no previous live birth, who had vaginal delivery, and a positive result at antenatal GBS screening. Despite satisfactory GBS screening implementation, there is still a substantial gap between optimal and actual IAP. We hypothesize that the complexity of the CDC guidelines may partially explain this shortcoming. Future efforts will include initiatives focused at enabling and reinforcing adherence to evidence-based prevention practices.
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Project description:BackgroundGroup B Streptococcus (GBS) is the leading cause of neonatal sepsis and meningitis worldwide. We aimed to estimate the current burden of neonatal invasive GBS disease in the Netherlands, as a first step in providing an evidence base for policy makers on the potential benefits of a future maternal GBS vaccine.MethodsSurveillance of neonatal invasive GBS occurs at the National Reference Laboratory for Bacterial Meningitis, where culture isolates from cerebrospinal fluid and blood are sent by diagnostic laboratories. From the number of cultures we estimated the incidence of neonatal (age 0-90 days) GBS meningitis and sepsis. We constructed a disease progression model informed by literature and expert consultation to estimate the disease burden of neonatal invasive GBS infection. As many neonates with a probable GBS sepsis are never confirmed by blood culture, we further estimated the disease burden of unconfirmed cases of probable GBS sepsis in sensitivity analyses.ResultsAn estimated 97 cases and 6.5 deaths occurred in the Netherlands in 2017 due to culture positive neonatal invasive GBS infection. This incidence comprised 15 cases of meningitis and 42 cases of sepsis per 100.000 births, with an estimated mortality of 3.8 per 100.000 live births. A disease burden of 780 disability-adjusted life years (DALY) (95% CI 650-910) or 460 DALY per 100.000 live births was attributed to neonatal invasive GBS infection. In the sensitivity analysis including probable neonatal GBS sepsis the disease burden increased to 71 cases and 550 DALY (95% CI 460-650) per 100.000 live births.ConclusionIn conclusion, neonatal invasive GBS infection currently causes a substantial disease burden in the Netherlands. However, important evidence gaps are yet to be filled. Furthermore, cases of GBS sepsis lacking a positive blood culture may contribute considerably to this burden potentially preventable by a future GBS vaccine.
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Project description:Streptococcus thermophilus, a gram-positive facultative anaerobe, is one of the most important lactic acid bacteria widely used in the dairy fermentation industry. In this study, we have analyzed the global transcriptional profiling of S. thermophilus upon temperature change. During a temperature shift from 42°C to 50°C, it is found that 196 (10.4%) genes show differential expression with 102 up-regulated and 94 down-regulated at 50°C. In particular, 1) Heat shock genes, such as DnaK, GroESL and clpL, are identified to be elevated at 50°C; 2) Transcriptional regulators, such as HrcA, CtsR, Fur, MarR and MerR family, are differentially expressed, indicating the complex molecular mechanisms of S. thermophilus adapting to heat shock; 3) Genes associated with signal transduction, cell wall genes, iron homeostasis, ABC transporters and restriction-modification system were induced; 4) A large number of the differentially expressed genes are hypothetical genes of unknown function, indicating that much remains to be investigated about the heat shock response of S. thermophilus. Experimental investigation of selected heat shock gene ClpL shows that it plays an important role in the physiology of S. thermophilus at high temperature and meanwhile we confirmed ClpL as a member of the CtsR regulon. Overall, this study has contributed to the underlying adaptive molecular mechanisms of S. thermophilus upon temperature change and provides a basis for future in-depth functional studies.
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