Investigating the role of Rgg1518 transcriptional regulator in Streptococcus pneumoniae biology
Ontology highlight
ABSTRACT:
ORGANISM(S): Streptococcus pneumoniae D39
PROVIDER: GSE154887 | GEO | 2021/06/01
REPOSITORIES: GEO
Similar Datasets
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
Project description:Purpose: Key steps in understanding a biological process include identifying genes that are involved and determining how they are regulated. We developed a novel method for identifying TFs involved in a specific process and used it to map regulation of the key virulence factor of Cryptococcus neoformans, its capsule. Results: The map, built from expression profiles of 41 TF mutants, includes 20 TFs not previously known to regulate virulence attributes. It also reveals a hierarchy comprising executive, mid-level, and “foreman” TFs. When grouped by temporal expression pattern, these TFs explain much of the transcriptional dynamics of capsule induction. Phenotypic analysis of 41 TF deletion mutants revealed complex relationships among virulence factors and virulence in mice. Conclusions: These data resources and analyses provide the first integrated, systems level view of capsule regulation and biosynthesis. Our methods dramatically improve the efficiency with which transcriptional networks can be analyzed, making genomic approaches accessible to labs focused on specific physiological processes. A total of 288 expression profiles were generated by RNA-Seq analysis of Mutant and wildtype cells grown in capsule inducing conditions for 90 minutes. In addition, 3 replicate expression profiles were generated for wildtype cells grown in : a capsule non-inducing condition, a capsule inducing condition for 180 minutes, a capsule inducing condition for 480 minutes, and a capsule inducing condition for 1440 minutes. In addition, ChIP-seq of NRG1(CNAG_05222) in capsule inducing conditions, and USV101(CNAG_05420) in both capsule inducing and non-inducing conditions were generated.
2015-01-14 | E-GEOD-60398 | biostudies-arrayexpress
Project description:In this study, we used transcriptional profiling to define the adaptive response of C. violaceum to oxidative stress induced by cumene hydroperoxide (CHP) and to identify the OhrR regulon. DNA microarray and northern blot analysis revealed that in CHP-treated cells occur strong upregulation of genes involved in many pathways for stress protection, including antioxidant enzymes (catalase and peroxidases), thioredoxin, glutaredoxin and lipoyl-dependent reducing systems, DNA repair enzymes, heat shock response (σ32 regulon), iron limitation (Fur regulon) and nitrogen starvation. Genes encoding glyoxalases, glutathione S-transferases and oxygenases were also induced, suggesting further catabolism of the aromatic compound CHP. Pathways downregulated by CHP stress include electron transport chain, nucleotide biosynthesis and unsaturation of fatty acids. Further, we identified two upregulated genes (OhrA and a protein with GGDEF domain for c-di-GMP synthesis) and three downregulated genes (hemolysin, chitinase and collagenase) in the ohrR mutant. Using a mouse infection model, we demonstrate that the ohrR mutant, but not the ohrA mutant, is attenuated for virulence and showed a decreased bacterial burden in the liver. Therefore, we have defined the CHP stimulon and determined that C. violaceum uses the organic hydroperoxide sensor OhrR for regulate expression of genes required to antioxidant defense and to modulate virulence in its interaction with the host.
2017-05-01 | GSE90551 | GEO
Project description:Plant cell wall degrading enzymes (PCWDEs) are key virulence determinants in the pathogenesis of the potato pathogen, Pectobacterium atrosepticum. In this study, we report the impact on virulence of a transposon insertion mutation in the metJ gene that codes for the repressor of the methionine biosynthesis regulon. In a mutant strain defective for the small regulatory RNA rsmB, PCWDEs are not produced and virulence in potato tubers is almost totally abolished. However, when the metJ gene is disrupted in this background, the rsmB- phenotype is suppressed and virulence and PCWDE production are restored. Additionally, when metJ is disrupted, production of the quorum sensing signal, N-(3-oxohexanoyl)-homoserine lactone, is induced precociously. The metJ mutant strains showed pleiotropic transcriptional impacts affecting approximately a quarter of the genome. Genes involved in methionine biosynthesis were most highly up-regulated, but many virulence-associated transcripts were also upregulated. This is the first report of the impact of the MetJ repressor on virulence in bacteria.
2012-11-02 | E-MTAB-1167 | biostudies-arrayexpress
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:Purpose: Key steps in understanding a biological process include identifying genes that are involved and determining how they are regulated. We developed a novel method for identifying TFs involved in a specific process and used it to map regulation of the key virulence factor of Cryptococcus neoformans, its capsule. Results: The map, built from expression profiles of 41 TF mutants, includes 20 TFs not previously known to regulate virulence attributes. It also reveals a hierarchy comprising executive, mid-level, and “foreman” TFs. When grouped by temporal expression pattern, these TFs explain much of the transcriptional dynamics of capsule induction. Phenotypic analysis of 41 TF deletion mutants revealed complex relationships among virulence factors and virulence in mice. Conclusions: These data resources and analyses provide the first integrated, systems level view of capsule regulation and biosynthesis. Our methods dramatically improve the efficiency with which transcriptional networks can be analyzed, making genomic approaches accessible to labs focused on specific physiological processes.
2015-01-14 | GSE60398 | GEO
Project description:Background: Conflicting results have been reported about the role of the two-component sensor and transcriptional regulator DosS/DosR, controlling the expression of the dormancy DosR regulon, for in vivo virulence of M. tuberculosis. Here, we have used a new approach to further analyze the relevance of the dosRS system, by driving DosR (Rv3133c) expression under the control of a constitutive promoter (phsp60). Methodology/Principal Findings: M. tuberculosis H37Rv constitutively expressing the transcriptional regulator DosR (Mtb::DosR) was compared to wild type M. tuberculosis (Mtb+/+) for in vitro growth kinetics and expression of the target genes of the DosR dormancy regulon, for in vivo virulence and for immunogenicity in mice. Under aerobic conditions, hsp60-driven DosR induced the expression of 28 out of 39 tested DosR regulon genes. In vitro growth characteristics were comparable for both strains, but Mtb::DosR showed an attenuated in vivo phenotype in immunocompetent mice, as indicated by reduced bacterial replication, reduced pulmonary immunopathology, reduced cachexia and significantly prolonged survival time as compared Mtb+/+. In immunodeficient SCID mice, Mtb::DosR was fully virulent. RT-qPCR analysis revealed a strong and comparable pulmonary TNF-?? and IL-23 expression following intratracheal infection, whereas IL-12 and IL-17 expression was slightly higher with wild type Mtb+/+. Finally, mice persistently infected with Mtb::DosR for 8 months showed five to tenfold higher lung IFN-?? responses against ten of the 48 DosR regulon encoded antigens (Rv1733c, Rv1734, Rv1738, Rv1996, Rv1997, Rv2029c, Rv2623, Rv2627c, Rv2628 and Rv3127) than mice actively infected with Mtb+/+. In spleen however, DosR regulon encoded antigen specific IFN-?? responses were similar in both groups. Conclusions/Significance. Collectively, these results suggest that increased DosR regulon encoded antigen specific pulmonary T cell responses are responsible for the attenuated phenotype of Mtb::DosR and that infection with Mtb::DosR could be used as a new animal model for studying key aspects of latent tuberculosis. Set of arrays that are part of repeated experiments
2012-06-12 | E-GEOD-19838 | biostudies-arrayexpress
Project description:A fliZ mutant in the entomopathogenic bacterium X. nematophila is attenuated in virulence in the insect. The goal of this study is to compare transcriptomes of the fliZ mutant and wild type strain to identify the FliZ regulon.
2013-05-27 | GSE47365 | GEO
Project description:Pasteurella multocida is a Gram-negative capsulated bacterium responsible for a range of diseases that cause severe morbidity and mortality in livestock animals. The hyaluronic acid (HA) capsule produced by P. multocida serogroup A strains is a critical virulence factor. In this study, we utilised transposon-directed insertion site sequencing (TraDIS) to identify genes essential for in vitro growth of P. multocida, and combined TraDIS with discontinuous density gradients (TraDISort) to identify genes required for HA capsule production and regulation in this pathogen. Analysis of mutants with a high cell density phenotype, indicative of the loss of extracellular capsule, led to the identification of 69 genes important for capsule production. These genes included all previously characterized genes in the capsule biosynthesis locus, and fis and hfq that encode known positive regulators of P. multocida capsule. Many of the other capsule-associated genes identified in this study were involved in regulation or activation of the stringent response, including spoT and relA that encode proteins that regulate the concentration of guanosine alarmones. Disruption of the autoregulatory domains in the C-terminal half of SpoT using insertional mutagenesis resulted in reduced expression of capsule biosynthesis genes and an acapsular phenotype. Overall, these findings have greatly increased the understanding of hyaluronic acid capsule production and regulation in P. multocida.
2022-03-14 | GSE198087 | GEO
Project description:Streptococcus pneumoniae (Spn), a Gram-positive bacterium, poses a significant threat to human health, causing mild respiratory infections to severe invasive conditions. Despite availability of vaccines, challenges persist due to serotype replacement and antibiotic resistance, emphasizing the need for alternative therapeutic strategies. This study explores the intriguing role of polyamines, ubiquitous, small organic cations, in modulating virulence factors, especially the capsule, a crucial determinant of Spn's pathogenicity. Utilizing chemical inhibitors, difluoromethylornithine (DFMO) and AMXT 1501, this research unveils distinct regulatory effects on the gene expression of Spn D39 serotype in response to altered polyamine homeostasis. DFMO inhibits polyamine biosynthesis, disrupting pathways associated with glucose import and interconversion of sugars. In contrast, AMXT 1501, targeting polyamine transport, enhances the expression of polyamine and glucose biosynthesis genes, presenting a novel avenue for regulating the capsule independent of glucose availability. Despite ample glucose availability, AMXT 1501 treatment downregulates glycolytic pathway, fatty acid synthesis and ATP synthase, crucial for energy production while upregulating two-component systems responsible for stress management. This suggests a potential shutdown of energy production and capsule biosynthesis, redirecting resources towards stress management. Following DFMO and AMXT 1501 treatments, countermeasures such as upregulation of stress response genes and ribosomal protein were observed but appear to be insufficient to overcome the deleterious effects on capsule production. This study highlights the complexity of polyamine-mediated regulation in S. pneumoniae, particularly, capsule biosynthesis. Our findings offer valuable insights into potential therapeutic targets for modulation of capsule in a polyamine dependent manner, a promising avenue for intervention against S. pneumoniae infections.
2024-02-28 | GSE252370 | GEO