Defense Hotspots
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB47940 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:A collection of 61 Salmonella enterica serovar Typhimurium (S. Typhimurium) of animal and human origin, matched as closely as possible by phage type, antimicrobial resistance pattern and place / time of isolation, and sourced from farms or hospitals in Scotland, were analysed by antimicrobial susceptibility testing, phage typing, pulsed field gel electrophoresis (PFGE), plasmid profiling and DNA microarrays. PFGE of all 61 isolates revealed ten PFGE profiles, which clustered by phage type and antibiotic resistance pattern, with human and animal isolates distributed between PFGE profiles. Analysis of 23 representative S. Typhimurium strains hybridised to a composite Salmonella DNA microarray identified a small number of specific regions of genome variation between different phage types and PFGE profiles. These variable regions of DNA were typically located within prophage-like elements. Simple PCR assays were subsequently designed to discriminate between different isolates from the same geographical region.
2007-06-09 | E-SGRP-6 | biostudies-arrayexpress
Project description:Staphylococcus aureus is a Gram-positive human pathogen causing a variety of human diseases in both hospital and community settings. This bacterium is so closely associated with prophages that it is rare to find S. aureus isolates without prophages. Two phages are known to be important for staphylococcal virulence: the beta-hemolysin (hlb) converting phage and the Panton-Valentine Leukocidin (PVL) converting phage. The hlb-converting phage is found in more than 90% of clinical isolates of S. aureus. This phage produces exotoxins and immune modulatory molecules, which inhibit human innate immune responses. The PVL-converting phage produces the two-component exotoxin PVL, which can kill human leucocytes. This phage is wide-spread among community-associated methicillin resistant S. aureus (CA-MRSA). It also shows strong association with soft tissue infections and necrotizing pneumonia. Several lines of evidence suggest that staphylococcal prophages increase bacterial virulence not only by providing virulence factors but also by altering bacterial gene expression: 1) Transposon insertion into prophage regulatory genes, but not into the genes of virulence factors, reduced S. aureus killing of Caenorhabditis elegans.; 2) Although the toxins and immune modulatory molecules encoded by the hlb- converting phages do not function in the murine system, deletion of ϕNM3, the hlb-converting phage in S. aureus Newman, reduced staphylococcal virulence in the murine abscess formation model. 3) In a preliminary microarray experiment, prophages in S. aureus Newman altered the expression of more than 300 genes. In this research proposal, using microarray and high-throughput quantitative RT-PCR (qRT-PCR) technologies, we will identify the effects of the two important staphylococcal phages on the gene expression of S. aureus in both in vitro and in vivo conditions. This project is intended to be completed within one year. All the data – microarray, qRT-PCR and all the primer sequences- will be made available to public 6 month after completion. Data from this project will help us to understand the role of prophages in the S. aureus pathogenesis and can lead to development of a strategy to interfere with the pathogenesis process. Following strains were grown in TSA broth: Staphylococcus aureus USA300 (reference) Staphylococcus aureus USA300 with deletion of ϕSa2usa (Query) Staphylococcus aureus USA300 with deletion of ϕSa3usa (Query) Staphylococcus aureus USA300 Prophage-free mutant (Query) Staphylococcus aureus USA300 Prophage-free mutant lysogenized with ϕSa2mw (Query) Staphylococcus aureus USA300 Prophage-free mutant lysogenized with ϕSa3usa (Query) strain: Staphylococcus aureus USA300 Prophage-free mutant lysogenized with both ϕSa2mw and ϕSa3usa (Query) RNA samples were harvested at early log, midlog and stationary phase.Samples were hybridized on aminosilane coated slides with 70-mer oligos.
2011-02-28 | E-GEOD-26623 | biostudies-arrayexpress
Project description:Staphylococcus aureus (S. aureus) is a known pathogen able to infect humans and animals. Human S. aureus isolates are often associated with carriage of Sa3int prophages combined with loss of beta-hemolysin production due to gene disruption, whereas animal isolates are positive for beta-hemolysin associated with absence of Sa3int prophages. Sa3int prophages are known to contribute to staphylococcal fitness and virulence in human host by providing human-specific virulence factors encoded on the prophage genome. Strain-specific differences in regard to phage transfer, lysogenization and induction are attributable to yet unknown staphylococcal factors specifically influencing prophage gene expression. In this work we used tagRNA-sequencing approach to specifically search for these unknown host factors and differences in prophage gene expression. For this purpose, we established a workflow revealing the first direct comparison for differential gene expression analysis on two distinct single-lysogenic S. aureus isolates. Further, global gene expression patterns were investigated in two S. aureus isolates upon mitomycin C treatment and compared to uninduced conditions. This provides new insights into the tightly linked host-phage interaction network.
2022-10-03 | GSE214523 | GEO
Project description:Meiotic recombination, crucial for proper chromosome segregation and genome evolution, is initiated by programmed DNA double-strand breaks (DSBs) in budding and fission yeasts and likely all sexually reproducing species. In fission yeast, DSBs occur up to several hundred times more frequently at special sites, called hotspots, than in other regions of the genome. What distinguishes hotspots from cold regions is a major unsolved problem, although transcription factors determine some hotspots. We report here the discovery that three coiled-coil proteins -- Rec25, Rec27, and Mug20 -- bind essentially all hotspots with unprecedented, high specificity even without DSB formation. These small proteins are components of linear elements, are related to synaptonemal complex proteins, and are essential for nearly all DSBs at most hotspots. Our results indicate that these hotspot determinants activate or stabilize the DSB-forming protein Rec12 (Spo11 homolog) rather than promote its binding to hotspots. We propose here a new paradigm for hotspot determination and crossover control by linear element proteins.
2012-12-26 | GSE43121 | GEO
Project description:Meiotic recombination, crucial for proper chromosome segregation and genome evolution, is initiated by programmed DNA double-strand breaks (DSBs) in budding and fission yeasts and likely all sexually reproducing species. In fission yeast, DSBs occur up to several hundred times more frequently at special sites, called hotspots, than in other regions of the genome. What distinguishes hotspots from cold regions is a major unsolved problem, although transcription factors determine some hotspots. We report here the discovery that three coiled-coil proteins -- Rec25, Rec27, and Mug20 -- bind essentially all hotspots with unprecedented, high specificity even without DSB formation. These small proteins are components of linear elements, are related to synaptonemal complex proteins, and are essential for nearly all DSBs at most hotspots. Our results indicate that these hotspot determinants activate or stabilize the DSB-forming protein Rec12 (Spo11 homolog) rather than promote its binding to hotspots. We propose here a new paradigm for hotspot determination and crossover control by linear element proteins.
2012-12-26 | GSE43118 | GEO
Project description:Quorum sensing (QS) is the cell density-dependent virulence factor regulator in Pseudomonas aeruginosa. Here, we elucidate PIT2, a phage-encoded inhibitor of the QS regulator LasR, derived from the lytic Pseudomonas phage LMA2. PIT2 inhibits the effectors PrpL and LasA of the type 2 secretion system of P. aeruginosa and attenuates bacterial virulence towards HeLa cells and in Galleria mellonella. Using RNAseq-based differential gene expression analysis, the effect of PIT2 on the LasR regulatory network was revealed. Moreover, the specific interaction between LasR and PIT2 was determined. These data expand our knowledge on phage-encoded modulators of the bacterial metabolism, as this examples an anti-virulence protein derived from a lytic phage. From an applied perspective, this phage protein reveals and exploits an interesting anti-virulence target in P. aeruginosa. As such, it lays the foundation for a new phage-inspired anti-virulence strategy to combat multidrug resistant pathogens and opens the door for SynBio applications.
2023-09-27 | GSE227677 | GEO
Project description:Here we have used a combination of advanced proteomics and genomics approaches to investigate the extent and mechanisms of transcription factor cross-talk at genomic hotspots. We identify ~12,000 transcription factor hotspots in the early phase of adipogenesis, and we find evidence of both simultaneous and sequential binding of transcription factors at these regions. We demonstrate for the first time that hotspots are highly enriched in large super-enhancer regions and that these drive the early adipogenic reprogramming of gene expression. Our results indicate that cooperativity between transcription factors at the level of hotspots as well as super-enhancers is very important for enhancer activity and transcriptional reprogramming. Thus, hotspots and super-enhancers constitute important regulatory hubs integrating external stimuli on chromatin.
2014-04-17 | GSE56872 | GEO
Project description:Histone modifications are associated with meiotic recombination hotspots, discrete sites with augmented recombination frequency. For example, trimethylation of histone H3 lysine4 (H3K4me3) marks most hotspots in budding yeast and mouse. Modified histones are known to regulate meiotic recombination partly by promoting DNA double strand break (DSB) formation, but the role and precise landscape of histone modifications at hotspots remain unclear. Here, we studied hotspot-associated modifications in fission yeast and found general features: acetylation of H3 lysine9 (H3K9ac) is strikingly elevated, and H3K4me3 is not significantly enriched. Remarkably, elimination of H3K9ac reduced binding of the DSB-inducing enzyme Rec12 and DSB at hotspots. We also found that the H3K4 metyltransferase Set1 promotes DSB formation at some loci, but it restricts Rec12 binding to hotspots. These results suggest that H3K9ac rather than H3K4me3 is a hotspot-associated mark involved in meiotic DSB formation in fission yeast. S.pombe cells in a pat1-114 background were induced to enter meiosis by the haploid meiosis system, and harvested one hour after the induction. ChIP were performed using anti-H3Cter, H3K9ac, -H3K14ac and -H3K4me3 antibodies. pat1-114 rad50S rec12+-FLAG cells in a wild type, H3K9A or set1+ deletion background were induced to enter meiosis by the haploid meiosis system, and harvested five hours after the induction. ChIP were performed using anti-FLAG antibodies.
2013-03-07 | E-GEOD-31648 | biostudies-arrayexpress
Project description:Mammalian genetic recombination is concentrated at hotspots, specialized 1-2 Kb sites separated by long stretches of DNA lacking recombination. Mammalian hotspot locations depend on PRDM9, a zinc finger protein that binds at hotspots and uses its SET domain to locally trimethylate histone H3K4. Here we find that PRDM9 also locally trimethylates H3K36 at hotspots. Using ChIP-seq and immunoprecipitation data for H3K36me3 in murine spermatocytes, we show that H3K4me3 and H3K36me3 coincide only at hotspots in germ cells, and that this H3K4me3/H3K36me3-double-positive signature is almost entirely dependent on PRDM9. We performed ChIP-seq with an antibody against H3K36me3, using chromatin extracted from murine spermatocytes, and compared it to previously generated ChIP-seq data for H3K4me3 in the same cell type. ---------------------------------- This dataset represents the H3K36 component only
2016-06-30 | E-GEOD-76416 | biostudies-arrayexpress
Project description:During infection, transcriptional changes in both the phage and its host bacterium influence the outcome of infection. The xenobiotic response element (XRE) family of transcription factors (TFs), which are commonly encoded by bacteria and phages, regulate diverse aspects of bacterial cell physiology and can impact phage infection dynamics. Through a pangenome analysis of Caulobacter species isolated from soil and aquatic ecosystems, we uncovered an apparent radiation of an XRE TF gene cluster, several of which have established functions in the regulation of holdfast adhesin development and biofilm formation in C. crescentus. We further discovered related XRE TFs across the class Alphaproteobacteria and its phages, including the φCbK Caulophage, suggesting that members of this gene cluster impact host-phage interactions. Here we show that that a closely related group of XRE proteins, encoded by both C. crescentus and φCbK, can interact to form heteromeric associations and control the transcription of a common gene set, influencing processes such as adhesin development and the progression of φCbK infection. The φCbK XRE paralog, tgrL, is highly expressed at the earliest stages of infection and can directly repress transcription of hfiA, a potent adhesion factor, and gafYZ, a transcriptional activator of prophage-like gene transfer agents (GTAs) encoded on the C. crescentus chromosome. A group of C. crescentus XRE proteins also directly repress gafYZ transcription, revealing a functionally redundant set of host regulators that may protect against spurious production of GTA particles and inadvertent cell lysis. Deleting host XRE transcription factors reduced φCbK burst size, while overexpressing these genes or φCbK tgrL rescued this burst defect. We conclude that a large XRE TF gene cluster, shared by C. crescentus and φCbK, plays an important role in adhesion regulation under phage-free conditions, and influences host-phage dynamics during infection.
2023-08-25 | GSE241053 | GEO