Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Activation by CcpA-FDP of two key determinants of pneumococcal virulence, capsule production and choline utilization.

ABSTRACT: The kinetic behaviour of S. pneumoniae during vaccine production was studied using a dynamic systemic approach. Quantification of key intracellular glycolytic metabolites coupled to global transcriptomic analysis led to an improved knowledge of pneumococcal physiology. In controlled growth conditions, a direct correlation between the accumulation of key glycolytic intermediates and the expression of capsular polysaccharide genes (cps operon encoding the main pneumococcal antigen) was established. Interestingly, the same correlation was confirmed for the genes involved in the assimilation and the modification of choline, an indispensable nutritional requirement for both growth and virulence of S. pneumoniae. Such a correlation suggests a direct or indirect control of the expression of these genes by the global transcriptional regulator CcpA (catabolite control protein A) since putative cre sites upstream of the promoter were identified, even though the exact nature of this regulation remains to be confirmed. Preliminary results indicate that a ccpA mutation provokes a significant decrease in the expression of these genes. The global transcriptomic analysis coupled with motif research has revealed an extended CcpA regulon in S. pneumoniae including genes involved in diverse metabolic functions. Keywords: Capsular polysaccharide industrial production

ORGANISM(S): Streptococcus pneumoniae

PROVIDER: GSE9670 | GEO | 2008/12/01

SECONDARY ACCESSION(S): PRJNA103553

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Activation by CcpA-FDP of two key determinants of pneumococcal virulence, capsule production and choline utilization.

Project description:The kinetic behaviour of S. pneumoniae during vaccine production was studied using a dynamic systemic approach. Quantification of key intracellular glycolytic metabolites coupled to global transcriptomic analysis led to an improved knowledge of pneumococcal physiology. In controlled growth conditions, a direct correlation between the accumulation of key glycolytic intermediates and the expression of capsular polysaccharide genes (cps operon encoding the main pneumococcal antigen) was established. Interestingly, the same correlation was confirmed for the genes involved in the assimilation and the modification of choline, an indispensable nutritional requirement for both growth and virulence of S. pneumoniae. Such a correlation suggests a direct or indirect control of the expression of these genes by the global transcriptional regulator CcpA (catabolite control protein A) since putative cre sites upstream of the promoter were identified, even though the exact nature of this regulation remains to be confirmed. Preliminary results indicate that a ccpA mutation provokes a significant decrease in the expression of these genes. The global transcriptomic analysis coupled with motif research has revealed an extended CcpA regulon in S. pneumoniae including genes involved in diverse metabolic functions. Keywords: Capsular polysaccharide industrial production One condition experiment examining the transcriptome between two growth phases of the same serotype (slide 1 to slide 4). Thus, cross analysis between the two serotypes during exponential growth was performed in order to complete the analysis

2010-05-15 | E-GEOD-9670 | biostudies-arrayexpress

An antibody to Streptococcus pneumoniae capsular polysaccharide enhances quorum sensing

Project description:The primary mechanism by which pneumococcal capsular polysaccharide-based vaccines are believed to mediate protection is by induction of serotype-specific opsonic antibodies that facilitate bacterial killing by phagocytes (opsonophagocytosis). However, antibodies that are protective against experimental pneumococcal pneumonia in mice but do not promote opsonophagocytic killing in vitro have also been identified 1-3. Such non-opsonic antibodies are associated with bacterial clearance in vivo, but the mechanism by which this occurs is unknown. In this letter, we demonstrate that a protective, non-opsonic serotype 3 pneumococcal capsular polysaccharide-specific monoclonal antibody (MAb) enhances quorum sensing, which results in competence induction and fratricide of serotype 3 pneumococcus. Gene expression profile analysis revealed that the MAb together with the pneumococcal autoinducer, competence stimulating peptide 2 (CSP2), augments differential expression of competence (com) related bacteriocin-like peptide (blp) genes that are known to be involved in pneumococcal fratricide. Taken together, these findings reveal a previously unsuspected mechanism of antibody action, namely, enhancement of quorum sensing and bacterial fratricide. Given that this activity does not require phagocytes, antibodies that function accordingly may hold promise as adjuncts to current vaccines or as desired products of next generation pneumococcal vaccines. 6 samples

2011-03-01 | E-GEOD-27258 | biostudies-arrayexpress

An antibody to Streptococcus pneumoniae capsular polysaccharide enhances quorum sensing

2011-03-01 | GSE27258 | GEO

Polyamine synthesis effects capsule expression in Streptococcus pneumoniae TIGR4

Project description:Purpose: We recently reported that isogenic deletion of lysine decarboxylase (ΔcadA/SP_0916), an enzyme that catalyzes the biosynthesis of polyamine cadaverine in Streptococcus pneumoniae TIGR4 results in loss of capsular polysaccharide (CPS), which constitutes a novel mechanism of regulation of CPS. Here, we conducted RNA-Seq to elucidate molecular mechanisms of CPS regulation in polyamine synthesis impaired pneumococci. Result: Significantly differentially expressed genes in ΔcadA represent pneumococcal pathways involved in the biosynthesis of precursors for CPS and peptidoglycan. Conclusion: We establish a possible link and interchange between two cellular processes such as high energy demanding capsule production and oxidative stress responses in polyamine synthesis impaired pneumococci (ΔcadA).

2019-09-30 | GSE130511 | GEO

Glutamate dehydrogenase (GdhA) of S. pneumoniae is required for high temperature adaptation

Project description:During its progression from nasopharynx to other sterile and non-sterile niches of its human host, Streptococcus pneumoniae must cope with changes in temperature. We hypothesized that the pneumococcal temperature adaptation is an important facet of pneumococcal in host survival. Here we evaluate the effect of temperature on the phenotype of pneumococcus and the role of glutamate dehydrogenase (GdhA) during thermal stress adaptation associated with virulence and survival. Microarray analysis revealed a significant transcriptional response to temperature changes, affecting the expression of 132 and 119 genes at 34°C and 40°C, respectively, at mid-exponential growth phase relative to at 37ºC. One of the differentially regulated genes was gdhA, which is upregulated at 40°C while downregulated at 34°C relative to 37°C. Mutation of gdhA attenuated the growth, cell size, biofilm formation, pH survival, and virulence factor generation in a temperature dependent manner. Moreover, we identify that both D39 and ΔgdhA strains showed homo-lactic fermentation in glucose, however, ΔgdhA had higher formate production than D39 at all temperatures, which raised the hypothesis that gdhA involves in the regulation of pyruvate formate lyase (pflB) which is activated by catabolite control protein A (CcpA). In silico analysis pointed that a putative CcpA binding site (cre) was found in two proximal regions of -gdhA-coding sequence. The CcpA binding to the putative promoter region of gdhA was confirmed by EMSA. Furthermore, the transcriptional regulation of gdhA by CcpA, was temperature dependent. Finally, ΔgdhA grown at 34°C or 40°C was less virulent in Galleria mellonella infection model, suggesting that GdhA is required for pneumococcal virulence in fluctuating temperatures. These data demonstrated that temperature is an important parameter that affects physiology of S. pneumoniae and GdhA plays a significant role in temperature adaptation.

2021-11-24 | GSE154888 | GEO

Opaque vs Transparent transcriptome of Streptococcus pneumoniae serotype 2 strain D39

Project description:Invasive pneumococcal disease is preceded by asymptomatic colonization of the human nasopharynx by Streptococcus pneumoniae. Progression from colonization to invasion is a watershed in the host-pathogen interaction, and exposes the pneumococcus to markedly different microenvironments. This in turn, requires alterations in gene expression profile to adapt to the new niche. One apparent adaptive mechanism is reversible phase variation between “transparent” and “opaque” colony opacity phenotypes. Transparent phase variants colonize the nasopharynx more efficiently than opaque variants of the same strain, while opaque variants exhibit higher systemic virulence. Previous studies have reported quantitative differences in surface components such as the capsule, teichoic acid and certain surface proteins between the two phenotypes, but the underlying regulatory mechanism is not understood. In the present study, we found no differences in expression of key surface proteins between opaque and transparent variants of S. pneumoniae strain D39, but opaque cells produced five-fold more capsular polysaccharide. Subsequent microarray and real-time RT-PCR analysis showed no differences in capsule gene expression, but several genes involved in uridine monophosphate (UMP) biosynthesis were up-regulated in the opaque phenotype. This correlated with significant increases in the intracellular concentrations of both UMP and UDP-glucose, which are essential precursors for capsule biosynthesis. Our data suggest a novel mechanism for pneumococcal capsule regulation, in which rate-limiting precursor pathways are modulated rather than the capsule biosynthetic genes themselves. Keywords: Phase variants

2007-08-17 | GSE8797 | GEO

Transcriptome analysis of different concentrations of benzyl isothiocyanate against Staphylococcus aureus

Project description:In this study, we monitored the transcriptional changes of S. aureus by RNA-seq analysis to better understand the effect of benzyl isothiocyanate (BITC) on the virulence inhibition of S. aureus and determined the bacteriostatic effect of BITC at subinhibitory concentrations. Our results revealed that compared with the control group (SAC), the BITC-treated experimental group (SAQ_BITC) had 708 differentially expressed genes (DEGs), of which 333 genes were downregulated and the capsular polysaccharide (cp) was significantly downregulated. Furthermore, we screened five of the most virulent factors of S. aureus, including the capsular polysaccharide biosynthesis protein (cp5D), capsular polysaccharide synthesis enzyme (cp8F), thermonuclease (nuc), clumping factor (clf) and protein A (spa).

2019-10-29 | GSE139494 | GEO

Serotyping of Streptococcus pneumoniae based on capsular genes polymorphisms

Project description:Diagnostic primer extension assay to serotype Streptococcus pneumoniae. Assay validation. Background: Monitoring of Streptococcus pneumoniae serotype epidemiology is essential since serotype replacement is a concern when introducing new polysaccharide-conjugate vaccines. To simplify S. pneumoniae serotyping, a novel PCR-based automated microarray assay was developed to assist in the tracking of the serotypes. Results: Autolysin (lytA), pneumolysin (ply) and eight genes located in the capsular operon (cps) were amplified using multiplex PCR. This step was followed by a tagged fluorescent primer extension step targeting serotype-specific polymorphisms. The tagged primers were then hybridized to a microarray. Results were exported to an expert system that transforms genetic typing data into capsular serotype identification. The assay was validated on 166 cultured S. pneumoniae samples from 63 different serotypes as determined by the Quellung method. In addition, the assay was tested on clinical specimens including 43 cerebrospinal fluid samples from patients with meningitidis and 59 nasopharyngeal aspirates from bacterial pneumonia patients. The assay presented with no cross-reactivity for 24 relevant bacterial species found in these types of samples. The limit of detection for serotyping and S. pneumoniae detection was 100 genome equivalent per reaction. Conclusion: This automated assay is amenable to clinical testing and does not require any culturing of the samples. The assay will be useful for the evaluation of serotype prevalence changes after new conjugate vaccines introduction. 166 quellung serotyped strains and two negative controls

2013-12-31 | E-GEOD-45865 | biostudies-arrayexpress

ccpA mutant compared to D39 wild-type in Streptococcus pneumoniae in CDM + GLucose at transition-phase of growth (TS)

Project description:Comparison of Streptococcus pneumoniae D39 ccpA mutant compared to D39 wild type in CDM with glucose as sole carbon source to define the regulon of carbon catabolite control protein CcpA under this condition Details described in Carvalho SM, Kloosterman TG, Neves AR, Kuipers OP. CcpA Ensures Optimal Metabolic Fitness of Streptococcus pneumoniae. Plos One 2011

2011-10-01 | GSE31816 | GEO

ccpA mutant compared to D39 wild-type in Streptococcus pneumoniae in CDM + Glucose at MID-log growth phase

2011-10-01 | GSE31815 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data