Ontology highlight
ABSTRACT:
PROVIDER: PRJNA743132 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Disseminated gonococcal infection associated with Neisseria gonorrhoeae genotypes
| PRJEB52601 | ENA
Project description:The emergence of fully antimicrobial resistant Neisseria gonorrhoeae has led global public health agencies to identify a critical need for next generation anti-gonococcal pharmaceuticals. The development and success of these compounds will rely upon valid pre-clinical models of gonorrhoeae infection. We recently developed and reported the first model of upper genital tract gonococcal infection. During initial characterization, we observed significant reproductive cycle-based variation in infection outcome. When uterine infection occurred in the diestrus phase, there was significantly greater pathology than during estrus phase. The aim of this study was to evaluate transcriptional profiles of infected uterine tissue from mice in either estrus or diestrus phase in order to elucidate possible mechanisms for these differences. Genes and biological pathways with phase-independent induction during infection showed a chemokine dominant cytokine response to Neisseria gonorrhoeae. Despite general induction being phase-independent, this common anti-gonococcal response demonstrated greater induction during diestrus phase infection. Greater activity of granulocyte adhesion and diapedesis regulators during diestrus infection, particularly in chemokines and diapedesis regulators, was also shown. In addition to a greater induction of the common anti-gonococcal response, Gene Set Enrichment Analysis (GSEA) identified a diestrus-specific induction of type-1 interferon signaling pathways. This transcriptional analysis of murine uterine gonococcal infection during distinct points in the natural reproductive cycle provided evidence for a common anti-gonococcal response characterized by significant induction of granulocyte chemokine expression and high proinflammatory mediators. The basic biology of this host response to N. gonorrhoeae in estrus and diestrus is similar at the pathway level, but varies drastically in magnitude. Overlaying this, we observed type-1 interferon induction specifically in diestrus infection where greater pathology is observed. This supports recent work suggesting this pathway has a significant, possibly host-detrimental, function in gonococcal infection. Together these findings lay the groundwork for further examination of the role of interferons in gonococcal infection. Additionally, this work enables the implementation of the diestrus uterine infection model using the newly characterized host response as a marker of pathology and its prevention as a correlate of candidate vaccine efficacy and ability to protect against the devastating consequences of N. gonorrhoeae-associated sequelae. Murine microarrays were used to examine transcriptional differences underlying significantly different phenotypes associated with uterine N. gonorrhoeae infection in the estrus versus diestrus phases of the natural reproductive cycle.
2018-08-27 | GSE113962 | GEO
Project description:In Neisseria gonorrhoeae, Fur (ferric uptake regulator) protein regulates iron homeostasis gene expression through binding to conserved sequences in promoters of iron-responsive genes. We have expanded the gonococcal Fur regulon using a custom microarray to monitor iron-responsive gene expression throughout the growth curve combined with a genome-wide in silico analysis to predict Fur boxes (FB), and in vivo FuRTA assays to detect genes able to bind Fur. Keywords: time course: (1hr ,2hr, 3hr, 4hr)
2010-01-01 | GSE16352 | GEO
Project description:The immune response to Neisseria gonorrhoeae is poorly understood, but its extensive antigenic variability and resistance to complement are thought to allow it to evade destruction by the host’s immune defenses. We propose that N. gonorrhoeae also avoids inducing protective immune responses in the first place. We previously found that N. gonorrhoeae induces IL-17-dependent innate responses in mice and suppresses Th1/Th2-dependent adaptive responses in murine cells in vitro through the induction of TGF-β. In this study using a murine model of vaginal gonococcal infection, mice treated with anti-TGF-β antibody during primary infection showed accelerated clearance of N. gonorrhoeae with incipient development of Th1 and Th2 responses and diminished Th17 responses in genital tract tissue. Upon secondary reinfection, mice that had been treated with anti-TGF-β during primary infection showed anamnestic recall of both Th1 and Th2 responses, with the development of anti-gonococcal antibodies in serum and secretions, and enhanced resistance to reinfection. In knockout mouse strains defective in Th1 or Th2 responses, accelerated clearance of primary infection due to anti-TGF-β treatment was dependent on Th1 but not Th2 activity, whereas resistance to secondary infection resulting from anti-TGF-β treatment during primary infection was due to both Th1- and Th2-dependent memory responses. We propose that N. gonorrhoeae proactively elicits Th-17-driven innate responses that it can resist, and suppresses Th1/Th2-driven specific adaptive immunity that would protect the host. Blockade of TGF-β reverses this pattern of host immune responsiveness and facilitates the emergence of protective anti-gonococcal immunity.
2011-03-22 | GSE28055 | GEO
Project description:Comparison of the gene complements of 33 clinical isolates of Neisseria gonorrhoeae.
2006-12-13 | E-MEXP-514 | biostudies-arrayexpress
Project description:Regulation of gene expression by small non-coding RNAs (sRNAs) plays a critical role in bacterial response to physiological stresses. NrrF, a trans-acting sRNA in Neisseria meningitidis and Neisseria gonorrhoeae, has been shown in the meningococcus to indirectly control, in response to iron (Fe) availability, the transcription of genes encoding subunits of succinate dehydrogenase, a Fe-requiring enzyme. Given that in other organisms sRNAs target multiple mRNAs to control gene expression, we used a global approach to examine the role of NrrF in controlling gonococcal transcription. Three strains, including N. gonorrhoeae FA1090, an nrrF deletion mutant and a complemented derivative were examined using a custom CombiMatrix microarray to assess the role of this sRNA in controlling gene expression in response to Fe availability. In the absence of NrrF, mRNA half-lives increased for 12 genes in Fe-depleted growth conditions, compared to FA1090. Biological functions for the 12 genes controlled by NrrF included energy metabolism, oxidative stress, antibiotic resistance, amino acid synthesis and a regulatory protein whose functions are not fully understood, in addition to hypothetical proteins.
2013-09-27 | GSE48526 | GEO
Project description:Maintenance of an anaerobic respiratory system in the obligate human pathogen, Neisseria gonorrhoeae, suggests that an anaerobic lifestyle may be important during the course of infection. However, at this point there have been no studies analyzing the complete gonococcal transcriptome response to anaerobiosis. Here we performed deep sequencing to compare the gonococcal transcriptomes of aerobic and anaerobically grown cells. We found that the anaerobic stimulon in gonococci was large, and that 198 chromosomal genes were found to be differentially expressed. We also observed a large induction of genes encoded within the cryptic plasmid, pJD1. Secondary analysis of genes found to be differentially expressed by RNA-seq using translational-lacZ fusions or RT-PCR demonstrated the RNA-seq results to be very reproducible. Surprisingly, many genes of prophage origin were induced anaerobically, as well as several transcriptional regulators previously unknown to be involved in anaerobic growth. We also confirmed expression and regulation of a small RNA, likely a functional equivalent of fnrS in the Enterobacteriaceae family. Several novel factors were identified to be anaerobically regulated, as well as a large number of hypothetical proteins were induced. Two biological replicates of cells grown aerobically or anaerobically with nitrite were analyzed, for a total of four samples subject to SOLiD RNA sequencing.
2011-01-26 | E-GEOD-26444 | biostudies-arrayexpress
Project description:Samples were collected from infected male patients and RNA seq was used to determine the transcriptome of Neisseria gonorrhoeae both during infection and during growth in chemically defined media (CDM). Samples were also collected from infected female patients to determine the transcriptome differences between male and female infections.
2018-04-18 | GSE113290 | GEO
Project description:Maintenance of an anaerobic respiratory system in the obligate human pathogen, Neisseria gonorrhoeae, suggests that an anaerobic lifestyle may be important during the course of infection. However, at this point there have been no studies analyzing the complete gonococcal transcriptome response to anaerobiosis. Here we performed deep sequencing to compare the gonococcal transcriptomes of aerobic and anaerobically grown cells. We found that the anaerobic stimulon in gonococci was large, and that 198 chromosomal genes were found to be differentially expressed. We also observed a large induction of genes encoded within the cryptic plasmid, pJD1. Secondary analysis of genes found to be differentially expressed by RNA-seq using translational-lacZ fusions or RT-PCR demonstrated the RNA-seq results to be very reproducible. Surprisingly, many genes of prophage origin were induced anaerobically, as well as several transcriptional regulators previously unknown to be involved in anaerobic growth. We also confirmed expression and regulation of a small RNA, likely a functional equivalent of fnrS in the Enterobacteriaceae family. Several novel factors were identified to be anaerobically regulated, as well as a large number of hypothetical proteins were induced.
2011-01-26 | GSE26444 | GEO