Streptococcus pyogenes 06BA18369
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ABSTRACT:
PROVIDER: PRJNA170537 | ENA |
REPOSITORIES: ENA
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Project description:The nasopharynx and the skin are the major oxygen-rich anatomical sites for colonization by the human pathogen Streptococcus pyogenes (group A Streptococcus, GAS). To establish infection, GAS must survive oxidative stress generated during aerobic metabolism and the release of reactive oxygen species (ROS) by host innate immune cells. Glutathione is the major host antioxidant molecule while GAS is glutathione-auxotrophic. Here we report the molecular characterization of the ABC transporter substrate binding protein GshT in the GAS glutathione salvage pathway. We demonstrate that glutathione uptake is critical for aerobic growth of GAS and that impaired import of glutathione induces oxidative stress that triggers enhanced production of the reducing equivalent NADPH. Our results highlight the interrelationship between glutathione assimilation, carbohydrate metabolism, virulence factor production and innate immune evasion. Together, these findings suggest an adaptive strategy employed by extracellular bacterial pathogens to exploit host glutathione stores for their own benefit.
2022-04-04 | GSE198061 | GEO
Project description:The objective of this study was to investigate which genes are important for Streptococcus pyogenes during intracellular survival in human macrophages. Streptococcus pyogenes is an important human pathogen, which has recently gained recognition as an intracellular microorganism during the course of severe invasive infections such as necrotizing fasciitis. Although the surface anchored M protein has been identified as a pivotal factor affecting phagosomal maturation and S. pyogenes survival within macrophages, the overall transcriptional profile required for the pathogen to adapt and persist intracellularly is yet unknown. To address this, gene expression profiles of S. pyogenes within human macrophages were determined and compared to those of extracellular bacteria using customized microarrays and real-time qRT-PCR. In order to model the early phase of infection involving adaptation to the intracellular compartment, samples were collected 2h post-infection and within 2 h post infection, the expression of 145 streptococcal genes was significantly altered in the intracellular environment. The majority of differentially regulated genes were associated with metabolic and energy-dependent processes. Key upregulated genes in early phase intracellular bacteria were ihk and irr, encoding a two-component gene regulatory system (TCS). We observed that an isogenic S. pyogenes mutant deficient in ihk/irr displayed significantly reduced bacterial counts as compared to wild-type bacteria following infection of macrophages. Comparison of gene expression of selected genes at 2h and 6h post-infection revealed a dramatic shift in response regulators over time with a down-regulation of ihk/irr genes concurrent with an upreguation of the well-studied covR/S two component regulator. In reinfection assays, intracellular bacteria from the 6h time point exhibited significantly greater survival within macrophages than did bacteria collected at the 2h time point. The findings illustrate how gene expression of S. pyogenes during the intracellular life cycle is fine-tuned by temporal expression of specific two-component systems.
2011-09-15 | GSE32130 | GEO
Project description:The biological basis of severe bacterial infection unveiling from heterogeneity induction
| PRJDB15476 | ENA
Project description:Streptococcus pyogenes is an obligate human pathobiont associated with many disease states. Here, we present a novel model of S. pyogenes infection using intact murine epithelium. From this model, we were able to perform RNA sequencing to evaluate the genetic changes undertaken by both the bacterium and host at 5 and 24 hours post infection. Analysis of these genomic data demonstrate that S. pyogenes undergoes significant genetic adaptation to successfully infect the murine epithelium, including changes to metabolism and activation of the Rgg2/Rgg3 quorum sensing (QS) system. Subsequent experiments demonstrate that an intact Rgg2/Rgg3 QS cascade is necessary to establish a stable superficial skin infection. Furthermore, activation of this pathway results in increased murine morbidity and increased bacterial burden on the skin. This phenotype is associated with gross changes to the murine skin, as well as histopathological evidence of inflammation. Taken together, these experiments offer a novel method to investigate S. pyogenes-epithelial interactions and demonstrate that a well-studied QS pathway is critical to a persistent infection.
2023-07-17 | GSE237018 | GEO
Project description:The objective of this study was to investigate which genes are important for Streptococcus pyogenes during intracellular survival in human macrophages. Streptococcus pyogenes is an important human pathogen, which has recently gained recognition as an intracellular microorganism during the course of severe invasive infections such as necrotizing fasciitis. Although the surface anchored M protein has been identified as a pivotal factor affecting phagosomal maturation and S. pyogenes survival within macrophages, the overall transcriptional profile required for the pathogen to adapt and persist intracellularly is yet unknown. To address this, gene expression profiles of S. pyogenes within human macrophages were determined and compared to those of extracellular bacteria using customized microarrays and real-time qRT-PCR. In order to model the early phase of infection involving adaptation to the intracellular compartment, samples were collected 2h post-infection and within 2 h post infection, the expression of 145 streptococcal genes was significantly altered in the intracellular environment. The majority of differentially regulated genes were associated with metabolic and energy-dependent processes. Key upregulated genes in early phase intracellular bacteria were ihk and irr, encoding a two-component gene regulatory system (TCS). We observed that an isogenic S. pyogenes mutant deficient in ihk/irr displayed significantly reduced bacterial counts as compared to wild-type bacteria following infection of macrophages. Comparison of gene expression of selected genes at 2h and 6h post-infection revealed a dramatic shift in response regulators over time with a down-regulation of ihk/irr genes concurrent with an upreguation of the well-studied covR/S two component regulator. In reinfection assays, intracellular bacteria from the 6h time point exhibited significantly greater survival within macrophages than did bacteria collected at the 2h time point. The findings illustrate how gene expression of S. pyogenes during the intracellular life cycle is fine-tuned by temporal expression of specific two-component systems. Five samples with three biological replicates are analysed. Each open reading frame in triplicate (three technical replicas per sample). Resulting in 6-9 data points per gene per condition. The extracellular bacteria are control samples and the internal control is the house-keeping gene gyrase.
2011-09-14 | E-GEOD-32130 | biostudies-arrayexpress
Project description:Background: The Scylla paramamosain is a very important aquaculture crustacean species in the southeast coastal areas of China including Shantou. For the past few years, mud crab cultured in Niutianyang of Shantou suffered from serious diseases, especially the bacterial diseases (such as Vibrio parahaemolyticus). In eukaryotes, small RNAs can regulate gene expression in post-transcription to act on host-pathogen interaction system. Aims: V.parahaemolyticus isolated from Shantou Niutianyang crab culture area was injected to S.paramamosains to carry out an essential analysis on global miRNA expression in diverse tissues between two groups by the Illumina Solex deep sequencing technology. Methodology:To examine the relationship between mud crab miRNA expression and the bacterial pathogen, we collected mixed two pools of equal amounts of RNA from 7 different mud crab tissues (mesenteron, heart, liver, gill, brain, muscle and blood) and sequencing by Illumine/Solexa deep sequencing technology under normal conditions and during infection with V.parahaemolyticus. The high throughput sequencing resulted in 19,144,358 and 18,559,070 raw reads corresponding to 17,496,577 and 16,888,096 high-quality mappable reads for the normal and infected mixed pools, respectively. Stem-loop RT-qPCRs were used to confirm the microRNAs expression in different tissues of two pools. The results show that miRNAs might play a key role in regulating gene expression during mud crab S.paramamosain infection with V.parahaemolyticus. Conclusions: We identified a large number of miRNAs during the mud crab Scylla paramamosain infection with V.parahaemolyticus, some of which are differentially expressed between the treatments and the controls. The study provides an opportunity for further understanding of small RNA function in the regulation of molecular response and gives us clues for further studies of the mechanisms of V.parahaemolyticus infection in mud crab.
2012-08-07 | GSE39921 | GEO
Project description:Background: The Scylla paramamosain is a very important aquaculture crustacean species in the southeast coastal areas of China including Shantou. For the past few years, mud crab cultured in Niutianyang of Shantou suffered from serious diseases, especially the bacterial diseases (such as Vibrio parahaemolyticus). In eukaryotes, small RNAs can regulate gene expression in post-transcription to act on host-pathogen interaction system. Aims: V.parahaemolyticus isolated from Shantou Niutianyang crab culture area was injected to S.paramamosains to carry out an essential analysis on global miRNA expression in diverse tissues between two groups by the Illumina Solex deep sequencing technology. Methodology:To examine the relationship between mud crab miRNA expression and the bacterial pathogen, we collected mixed two pools of equal amounts of RNA from 7 different mud crab tissues (mesenteron, heart, liver, gill, brain, muscle and blood) and sequencing by Illumine/Solexa deep sequencing technology under normal conditions and during infection with V.parahaemolyticus. The high throughput sequencing resulted in 19,144,358 and 18,559,070 raw reads corresponding to 17,496,577 and 16,888,096 high-quality mappable reads for the normal and infected mixed pools, respectively. Stem-loop RT-qPCRs were used to confirm the microRNAs expression in different tissues of two pools. The results show that miRNAs might play a key role in regulating gene expression during mud crab S.paramamosain infection with V.parahaemolyticus. Conclusions: We identified a large number of miRNAs during the mud crab Scylla paramamosain infection with V.parahaemolyticus, some of which are differentially expressed between the treatments and the controls. The study provides an opportunity for further understanding of small RNA function in the regulation of molecular response and gives us clues for further studies of the mechanisms of V.parahaemolyticus infection in mud crab. Examination of miRNA expression in normal Scylla paramamosain group and the Scylla paramamosain infected with Vibrio parahaemolyticus
2012-08-07 | E-GEOD-39921 | biostudies-arrayexpress
Project description:Streptococcus pyogenes (group A streptococci; GAS) is the main causative pathogen of monomicrobial necrotizing soft tissue infections (NSTIs). To resist immuno-clearance, GAS adapt their genetic information and/or phenotype to the surrounding environment. Hyper-virulent streptococcal pyrogenic exotoxin B (SpeB) negative variants caused by covRS mutations are enriched during infection. A key driving force for this process is the bacterial Sda1 DNase. Here, we identify another strategy resulting in SpeB-negative variants, namely reversible abrogation of SpeB secretion triggered by neutrophil effector molecules. Analysis of NSTI patient tissue biopsies revealed that tissue inflammation, neutrophil influx, and degranulation positively correlate with increasing frequency of SpeB-negative GAS clones. Using single colony proteomics, we show that GAS isolated directly from tissue express but do not secrete SpeB. Once the tissue pressure is lifted, GAS regain SpeB secreting function. Neutrophils were identified as the main immune cells responsible for the observed phenotype. Subsequent analyses identified hydrogen peroxide and hypochlorous acid as reactive agents driving this phenotypic GAS adaptation to the tissue environment. SpeB-negative GAS show improved survival within neutrophils and induce increased degranulation. Our findings provide new information about GAS fitness and heterogeneity in the soft tissue milieu and provide new potential targets for therapeutic intervention in NSTIs.
2023-10-24 | PXD040160 | Pride
Project description:We assessed alveolar bone changes of Collaborative cross (CC) lines in response to a mixed oral infection with a well-known periodontal pathogen. The CC lines showed significant variation in their response to the mixed infection. We then carried out RNA-seq analysis on periodontal tisuues of resistant CC lines, susceptible CC lines and two CC lines that showed bone formation after oral bacterial infection.
2020-02-19 | GSE145474 | GEO
Project description:Streptococcus pyogenes is a major causative agent of tonsillitis or pharyngitis in children, which can lead to more invasive infections and noninfectious sequellae. S. pyogenes can persist in tonsils, while one-third of children treated with antibiotics continue to shed streptococci and have recurrent infections. Mouse nasal-associated lymphoid tissue (NALT) is functionally analogous to human oropharangeal lymphoid tissues. The innate immune responses of naïve cells from a mucosal site to S. pyogenes is not well described; therefore, we infected C57BL/6 mice intranasally with 108 CFU S. pyogenes. Transcriptional responses by NALT after S. pyogenes infection were analyzed by Affymetrix microarray and quantitative RT-PCR. Wild-type S. pyogenes induces transcription of both type I and IFN-gamma-responsive genes, pro-inflammatory genes, and acute phase response plasma proteins within 24h after infection. Invasion of NALT and the induction of the interferon response were not dependent on expression of anti-phagocytic M1 protein. However, infection with an attenuated, less invasive mutant indicated that a robust innate response by NALT is significantly influenced by intra-NALT bacterial load. Granulocytic populations of NALT, cervical lymph nodes and spleen were discriminated by characteristic surface and intracellular markers. Intranasal infection induces systemic release of neutrophils and a substantial influx of neutrophils into NALT at 24h, which decline by 48h after infection. Macrophages do not significantly increase in S. pyogenes-infected NALT. Intranasal infection of IFN-gamma -/- (GKO) C57BL/6 mice did not lead to systemic dissemination of wild type S. pyogenes, despite reduced expression of IFN-gamma-responsive mRNAs in NALT. Infected GKO mice had an unregulated influx of neutrophils into NALT compared to immunocompetant mice and mice treated with an anti-IFN-gamma antibody more rapidly cleared S. pyogenes from NALT. Thus, IFN-gamma-induced responses have a suppressive influence on early clearance of this pathogen from NALT. Keywords: disease state analysis
2009-07-01 | GSE11494 | GEO