Extracellular phosphate is involved in the virulence regulation of Streptococcus pneumoniae
Ontology highlight
ABSTRACT:
ORGANISM(S): Streptococcus pneumoniae
PROVIDER: GSE221902 | GEO | 2023/11/30
REPOSITORIES: GEO
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Project description:Post-transcriptional gene regulation often involves RNA-binding proteins that modulate mRNA translation and/or stability either directly through protein-RNA interactions or indirectly by facilitating the annealing of small regulatory RNAs (sRNAs). The human pathogen Streptococcus pneumoniae D39 (pneumococcus) does not encode in its genome any homologs to RNA-binding proteins known to be involved in promoting sRNA stability and function, such as Hfq or ProQ, even though it contains genes for at least 112 sRNAs. Instead, the pneumococcal genome contains genes for at least six S1 RNA-binding domain proteins, which includes ribosomal protein S1 (rpsA), polynucleotide phosphorylase (pnpA), RNase R (rnr), and three proteins of unknown function. Here, we characterize the function of one of these conserved, yet uncharacterized S1-domain proteins, SPD_1366, which we have renamed CvfD (Conserved virulence factor D), since loss of this protein results in a attenuation of virulence in a murine pneumonia model. We also report that deletion of cvfD impacts expression of 144 transcripts including the pst1 operon, encoding the phosphate transport system 1 in S. pneumoniae. We further show that CvfD post-transcriptionally regulates the PhoU2 master regulator of the pneumococcal dual phosphate transport system by binding phoU2 mRNA and impacting translation. CvfD not only controls expression of phosphate transporter genes, but also functions as a global regulator impacting cold sensitivity and the expression of sRNAs and genes involved in diverse cellular functions, including manganese uptake and zinc efflux. Together, our data suggest that CvfD exerts a broad impact on pneumococcal physiology and virulence via post-transcriptional gene regulation.
2020-07-13 | GSE149546 | GEO
Project description:Post-transcriptional gene regulation often involves RNA-binding proteins that modulate mRNA translation and/or stability either directly through protein-RNA interactions or indirectly by facilitating the annealing of small regulatory RNAs (sRNAs). The human pathogen Streptococcus pneumoniae D39 (pneumococcus) does not encode in its genome any homologs to RNA-binding proteins known to be involved in promoting sRNA stability and function, such as Hfq or ProQ, even though it contains genes for at least 112 sRNAs. Instead, the pneumococcal genome contains genes for at least six S1 RNA-binding domain proteins, which includes ribosomal protein S1 (rpsA), polynucleotide phosphorylase (pnpA), RNase R (rnr), and three proteins of unknown function. Here, we characterize the function of one of these conserved, yet uncharacterized S1-domain proteins, SPD_1366, which we have renamed CvfD (Conserved virulence factor D), since loss of this protein results in a attenuation of virulence in a murine pneumonia model. We also report that deletion of cvfD impacts expression of 144 transcripts including the pst1 operon, encoding the phosphate transport system 1 in S. pneumoniae. We further show that CvfD post-transcriptionally regulates the PhoU2 master regulator of the pneumococcal dual phosphate transport system by binding phoU2 mRNA and impacting translation. CvfD not only controls expression of phosphate transporter genes, but also functions as a global regulator impacting cold sensitivity and the expression of sRNAs and genes involved in diverse cellular functions, including manganese uptake and zinc efflux. Together, our data suggest that CvfD exerts a broad impact on pneumococcal physiology and virulence via post-transcriptional gene regulation.
2020-07-01 | GSE148867 | GEO
Project description:Acetyl phosphate (AcP) is a small-molecule metabolite that can act as a phosphoryl group donor for response regulators of two-component regulatory systems (TCSs). Streptococcus pneumoniae (pneumococcus) synthesizes AcP by the conventional pathway involving the phosphotransacetylase and acetate kinase enzymes encoded by the pta and ackA genes, respectively. In addition, pneumococcus synthesizes copious amounts of AcP and hydrogen peroxide (H2O2) by the pyruvate oxidase enzyme encoded by spxB. To access possible roles of AcP in pneumococcal TCS regulation and metabolism, we constructed combinations of spxB, pta, and ackA mutants and determined their ATP, AcP, and H2O2 production. Epistasis and microarray experiments were consistent with a role for the AcP biosynthetic pathway in basal-level phosphorylation of WalRSpn and possibly other response regulators involved in sensing cell wall status. However, this basal phosphorylation likely does not play an active physiological role in sensing in S. pneumoniae.
2010-11-29 | GSE23404 | GEO
Project description:In our study, deletion of methionine synthesis gene metE (SPD_0510) impaired the growth of Streptococcus pneumoniae strain D39 significantly when bacteria were cultured in chemically defined medium with a low concentration of methionine. Bacteria undergo methionine starvation in this condition. We aimed to know how S. pneumoniae responses to methionine starvation, particularly at the transcriptional level. RNA-seq results show that 804 genes (41.2 % of whole genome) were differentially expressed under methionine starvation. Among them, 258 genes (32.1 %) are related to cell metabolism, with 75 genes involved in sugar and carbon metabolism, 88 genes for synthesis of metabolic products and 95 genes for uptake of amino acids and sugars. Combined with other experiments data, this showed the reprogrammed metabolism in S. pneumoniae under methionine starvation.
2022-04-01 | GSE184094 | GEO
Project description:Several genes involved in nitrogen metabolism are known to contribute to the virulence of pathogenic bacteria. Here, we studied the function of the nitrogen regulatory protein GlnR in the Gram-positive human pathogen Streptococcus pneumoniae. We demonstrate that GlnR mediates transcriptional repression of genes involved in glutamine synthesis and uptake (glnA, glnPQ), glutamate synthesis (gdhA), and the gene encoding the pentose phosphate pathway enzyme Zwf, which forms an operon with glnPQ. Moreover, the expression of gdhA is also repressed by the pleiotropic regulator CodY. The GlnR-dependent regulation occurs through a conserved operator sequence and is responsive to the concentration of glutamate, glutamine and ammonium in the growth medium. By means of in vitro binding studies and transcriptional analyses we show that the regulatory function of GlnR is dependent on GlnA. Mutants of glnA and glnP displayed significantly reduced adhesion to Detroit 562 human pharyngeal epithelial cells, suggesting a role for these genes in the colonization of the host by S. pneumoniae. Thus, our results provide a thorough insight into the regulation of glutamine and glutamate metabolism of S. pneumoniae as mediated by both GlnR and GlnA. Keywords: genetic modification
2006-06-23 | GSE5088 | GEO
Project description:Alterations in global transcriptional profiles of S. pneumoniae 6304 serotype 4 after 50 passages (50P) and 100 passages (100P) on laboratory media Keywords: Adaptation to unique growth environment
2009-05-29 | GSE12607 | GEO
Project description:Transcriptomic analysis of Streptococcus pneumoniae TIGR4 wildtype and it's isogenic ccpA mutant, grown in chemically defined media supplemented with physiological levels of carbohydrates to mimic the human nasopharynx and bloodstream. The goal is to examine how anatomical site-specific carbohydrate availability impacts S. pneumoniae physiology and virulence.
2021-11-18 | GSE189057 | GEO
Project description:The increasing rate of penicillin resistance in S. pneumoniae in the early 1970s has resulted in therapeutic challenges and has prompted the need for alternative therapy in the management of pneumococcal infections. The development of penicillin resistance has been documented to be as a result of altered penicillin binding protein which alters the binding capacity of the drug to the organism. We used microarrays to investigate other genes which may be involved in the development of penicillin resistance in S. pneumoniae and identified classes of genes on the surface of the organism which may contribute to resistance. Strains of S. pneumoniae with varying initial susceptibility to penicillin were selected. These strains were grown to the logarithmic phase before being exposed to subinhibitory concentration of penicillin. RNA was extracted before and after penicillin stress and hybridized on Affymetrix microarrays and represented as either Untreated (before penicillin stress) or treated (after penicillin stress). This was carried out for 3 representative strains; S676, I81, and R98. S, I, and R abbreviates Sensitive, Intermediate and resistant to Penicillin.
2010-05-13 | E-GEOD-21709 | biostudies-arrayexpress
Project description:spxB-encoded pyruvate oxidase is a major virulence factor of Streptococcus pneumoniae. During aerobic growth, SpxB synthesizes H2O2 and acetyl phosphate, which play roles in metabolism, signaling, and oxidative stress. We report here the first cis- and trans-acting regulatory elements for spxB transcription. These elements were identified in a genetic screen for spontaneous mutations that caused colonies of strain D39 to change from a semi-transparent to an opaque appearance. Six of the seven opaque colonies recovered (frequency 3x10-5) were impaired for SpxB function or expression. Two mutations changed amino acids in SpxB likely required for cofactor or subunit binding. One mutation defined a cis-acting adjacent direct repeat required for optimal spxB transcription. The other three spontaneous mutations created the same frameshift near the start of the trans-acting spxR regulatory gene. The SpxR protein contains helix-turn-helix, CBS, and HotDog domains implicated in binding DNA, adenosyl compounds, and CoA-containing compounds, respectively, and suggest that SpxR positively regulates spxB transcription in response to energy and metabolic state. Finally, microarray analyses of a spxR mutant demonstrated that SpxR positively regulates the strH exoglycosidase gene, which like spxB, has been implicated in colonization. Keywords: bacterial genetic modification
2008-01-04 | GSE9284 | GEO
Project description:Extracellular vesicles (EVs) have recently garnered attention for their participation in host-microbe interactions in Streptococcus pneumoniae infections. However, the effect of pEVs on the disruption of alveolar epithelial barrier remain poorly understood. Our studies focus on EVs produced by Streptococcus pneumoniae (pEVs), and reveal that pEVs are internalized by alveolar epithelial cells. In vitro, pEVs induce autophagy activation in a dosage-dependent manner and decrease the alveolar epithelial barrier’s trans-epithelium electrical resistance (TEER). In addition, pEV-containing bacterial peotein serine/threonine-protein kinase StkP may act as an activator for Streptococcus pneumoniae-induced autophagy activation. When administered systemically in mice, Streptococcus pneumoniae wild type strain induced acute lung injury, the deletion of stkP deletion strain attenuated this injury. Taken together, pEVs cargos emerge as critical contributors to tissue damage in mammalian hosts.
2023-12-13 | PXD046576 | Pride