Streptococcus pneumoniae
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PROVIDER: PRJNA103553 | ENA |
REPOSITORIES: ENA
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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
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
2008-12-01 | GSE9670 | GEO
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
Project description:Background The catabolite control protein A (CcpA) is a member of the LacI/GalR family of transcriptional regulators controlling carbon-metabolism pathways in low-GC Gram positive bacteria. It functions as a catabolite repressor or activator, allowing the bacteria to utilize the preferred carbon source over secondary carbon sources. This study is the first CcpA-dependent transcriptome and proteome analysis in S. aureus wild type and ccpA-deleted mutant, focussing on short-time effects of glucose under stable pH conditions. Results The addition of glucose to exponentially growing S. aureus increased enzymes of glycolytic pathway, indicating a higher glycolytic activity, while proteins required for the complete oxidation in the TCA cycle were repressed via CcpA. Phosphotransacetylase and acetate kinase, converting acetylCoA to acetate with a concomitant substrate-level phosphorylation were neither regulated by glucose nor by CcpA. Most CcpA directly repressed genes were involved in utilization of amino acids as secondary carbon sources. More genes were found to be differentially expressed by CcpA in a glucose-independent manner than in the classical, glucose dependent way, suggesting that glucose-independent regulation by CcpA may be of particular importance in S. aureus. In the presence of glucose, CcpA was found to regulate expression of genes involved in metabolism, but that of genes coding for virulence determinants. Conclusions This study identified the CcpA regulon of exponentially growing S. aureus, for the first time. As in other bacteria, the CcpA-regulon of S. aureus comprised a large amount of metabolic genes but also some 50 genes associated with virulence. CcpA seemed to work in a glucose- as well as glucose-independent way.
2008-12-20 | GSE12614 | GEO
Project description:Background. Pneumococcus is a major human pathogen and the polysaccharide capsule is considered its main virulence factor. Nevertheless, strains lacking a capsule, named non-typeable pneumococcus (NT), are maintained in nature and frequently colonise the human nasopharynx. Interest in these strains, not targeted by any of the currently available pneumococcal vaccines, has been rising as they seem to play an important role in the evolution of the species. Currently, there is a paucity of data regarding this group of pneumococci. Also, questions have been raised on whether they are true pneumococci. We aimed to obtain insights in the genetic content of NT and the mechanisms leading to non-typeability and to genetic diversity. Methods. A collection of 52 NT isolates representative of the lineages circulating in Portugal between 1997 and 2007, as determined by pulsed-field gel electrophoresis and multilocus sequence typing, was analysed. The capsular region was sequenced and comparative genomic hybridisation (CGH) using a microarray covering the genome of 10 pneumococcal strains was carried out. The presence of mobile elements was investigated as source of intraclonal variation. Results. NT circulating in Portugal were found to have similar capsular regions, of cps type NCC2, i.e., having aliB-like ORF1 and aliB-like ORF2 genes. The core genome of NT was essentially similar to that of encapsulated strains. Also, competence genes and most virulence genes were present. The few virulence genes absent in all NT were the capsular genes, type-I and type-II pili, choline-binding protein A (cbpA/pspC), and pneumococcal surface protein A (pspA). Intraclonal variation could not be entirely explained by the presence of prophages and other mobile elements. Conclusions. NT circulating in Portugal are a homogeneous group belonging to cps type NCC2. Our observations support the theory that they are bona-fide pneumococcal isolates that do not express the capsule but are otherwise essentially similar to encapsulated pneumococci. Thus we propose that NT should be routinely identified and reported in surveillance studies.
2014-11-24 | GSE58329 | GEO
Project description:Nonencapsulated Streptococcus pneumoniae (NESp) is an emerging human pathogen that colonizes the nasopharynx and is associated with noninvasive disease such as otitis media (OM), conjunctivitis, and nonbacteremic pneumonia. For decades, expression of a polysaccharide capsule appeared to be necessary for establishment of colonization and development of invasive pneumococcal disease (IPD). Accordingly, the currently licensed pneumococcal vaccines target the polysaccharide capsule. However, NESp expressing the novel oligopeptide importer proteins AliC and AliD have been isolated during IPD. Our study reveals that NESp expressing AliC and AliD have intensified virulence compared to isogenic mutants, and we provide insight about how this pneumococcal population has become associated with IPD. Our data demonstrates that AliC and AliD enhance murine nasopharyngeal colonization and are required for OM in a chinchilla model. Furthermore, AliC and AliD increase pneumococcal survival in chinchilla whole blood and decrease deposition of human C3b on the bacterial surface. As NESp become an increasing threat to public health, our study exposes specific virulence factors to possibly target for a broadened prevention of IPD through vaccination.
2018-01-22 | PXD005178 | Pride
Project description:Background The catabolite control protein A (CcpA) is a member of the LacI/GalR family of transcriptional regulators controlling carbon-metabolism pathways in low-GC Gram positive bacteria. It functions as a catabolite repressor or activator, allowing the bacteria to utilize the preferred carbon source over secondary carbon sources. This study is the first CcpA-dependent transcriptome and proteome analysis in S. aureus wild type and ccpA-deleted mutant, focussing on short-time effects of glucose under stable pH conditions. Results The addition of glucose to exponentially growing S. aureus increased enzymes of glycolytic pathway, indicating a higher glycolytic activity, while proteins required for the complete oxidation in the TCA cycle were repressed via CcpA. Phosphotransacetylase and acetate kinase, converting acetylCoA to acetate with a concomitant substrate-level phosphorylation were neither regulated by glucose nor by CcpA. Most CcpA directly repressed genes were involved in utilization of amino acids as secondary carbon sources. More genes were found to be differentially expressed by CcpA in a glucose-independent manner than in the classical, glucose dependent way, suggesting that glucose-independent regulation by CcpA may be of particular importance in S. aureus. In the presence of glucose, CcpA was found to regulate expression of genes involved in metabolism, but that of genes coding for virulence determinants. Conclusions This study identified the CcpA regulon of exponentially growing S. aureus, for the first time. As in other bacteria, the CcpA-regulon of S. aureus comprised a large amount of metabolic genes but also some 50 genes associated with virulence. CcpA seemed to work in a glucose- as well as glucose-independent way. The transcriptomes of strain Newman and its isogenic ccpA-deleted mutant were determined in early exponential growth and 30 min after the addition of 10 mM glucose, under controlled pH conditions. In the absence of glucose, the wild type grew slightly faster than the mutant, reaching an OD600 of 1 approximately 20 min earlier than the mutant. Adding 10 mM glucose at OD600 1 increased the growth rate of the wild type but had only a minor effect on that of the mutant. 60 min after glucose addition, glucose was depleted down to 0.3 mM by the wild type, while still 3 mM glucose was left in the culture of the mutant. Despite increased glucose consumption rates in the wild type, acetate production was only slightly enhanced compared to the mutant. No lactate was excreted at any time point sampled. Acidification of the medium upon glucose metabolism was prevented by buffering, maintaining a pH of 7.5 for both strains and under both growth conditions for at least 2 h after glucose addition, allowing to rule out any pH effects.
2010-06-24 | E-GEOD-12614 | biostudies-arrayexpress
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
Project description:Galactose is an important sugar for in vivo survival and virulence of important human pathogen Streptococcus pneumoniae, and pyruvate formate lyase (PFL) activity is crucial for galactose metabolism. Thus, the regulation of genes important for active PFL synthesis, pflA and pflB, was investigated. We identified six transcriptional regulators differentially expressed in ΔpflB and hypothesised that they are important for pflA or pflB regulation. Among these, CcpA, MerR2 and GntR family transcriptional regulators were directly involved in the regulation of pflA, pflB or both. It was found that CcpA is the transcriptional activator of pflB, and is the repressor of pflA on galactose. CcpA’s interaction with pflB did not require HPr-[Ser-P] but is enhanced by sodium formate, produced by the activity of PFL. The MerR2 is a repressor of both pflA and pflB, and sodium formate decreases MerR2 affinity for pflB promoter. In addition, MerR2 mediates ccpA expression mainly on glucose and to lesser degree on galactose, and MerR2 and CcpA interact for regulation of pflB. It was shown that both CcpA and MerR2 are required for pneumococcal colonisation and virulence. We also found that GntR represses pflB expression but its expression is not induced by any of the tested sugars, suggesting sugar independent regulation of pflB.
2017-01-26 | GSE67668 | GEO
Project description:Cryptococcus neoformans is an opportunistic basidiomycete pathogen that is a major etiological agent of fungal meningoencephalitis leading to more than 180,000 deaths worldwide annually. For this pathogen, the polysaccharide capsule is a key virulence factor, which interferes with the phagocytosis by host innate immune cells, but its complex signaling networks remain elusive. In this study, we systematically analyzed capsule biosynthesis and signaling networks by using C. neoformans transcription factor (TF) and kinase mutant libraries under diverse capsule-inducing conditions, such as Dulbecco’s Modified Eagle’s (DME), Littman’s medium (LIT) and fetal bovine serum (FBS) medium. We found that deletion of GAT201, YAP1, BZP4, and ADA2 consistently causes capsule production defects in all tested media, indicating that they are capsule-regulating core TFs. Epistatic and expression analysis showed that Yap1 and Ada2 control Gat201 upstream, whereas Bzp4 and Gat201 regulate capsule production independently. We next searched for potential upstream kinases and found that mutants deleted of PKA1, BUD32, POS5, IRE1 or CDC2801 showed reduced capsule production under all three capsule induction conditions, whereas mutants deleted of HOG1 and IRK5 displayed enhanced capsule production. Notably, Pka1 and Irk5 controls induction of GAT201 and BZP4, respectively, under capsule induction condition. Finally, we monitored transcriptome profiles governed by Bzp4, Gat201, and Ada2 under capsule-inducing condition and demonstrated that these TFs regulate redundant and unique sets of downstream target genes. In conclusion, this study provides further insight into the complex regulatory mechanism of capsule production related signaling pathways in C. neoformans.
2022-10-18 | GSE208163 | GEO