Bactericidal mechanism of hGIIA against streptococci
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ABSTRACT:
PROVIDER: PRJEB27626 | ENA |
REPOSITORIES: ENA
Dataset's files
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| ERR2683524.fastq.gz | Fastqsanger.gz |
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Project description:Secreted phospholipase A2-IIA (sPLA2-IIA) hydrolyzes phospholipids to liberate lysophospholipids and fatty acids. Given its poor activity toward eukaryotic cell membranes, its role in the generation of proinflammatory lipid mediators is unclear. Conversely, sPLA2-IIA efficiently hydrolyzes bacterial membranes. Here, we show that sPLA2-IIA impacts on the immune system by acting on the intestinal microbial flora. Using mice overexpressing transgene-driven human sPLA2-IIA, we found that the intestinal microbiota was critical for both induction of an immune phenotype and promotion of inflammatory arthritis. The expression of sPLA2-IIA led to alterations of the intestinal microbiota composition, but housing in a more stringent pathogen-free facility revealed that its expression could affect the immune system in the absence of changes to the composition of this flora. In contrast, untargeted lipidomic analysis focusing on bacteria-derived lipid mediators revealed that sPLA2-IIA could profoundly alter the fecal lipidome. The data suggest that a singular protein, sPLA2-IIA, produces systemic effects on the immune system through its activity on the microbiota and its lipidome.
2021-11-25 | GSE189441 | GEO
Project description:The interaction of secreted phospholipase A2-IIA with the microbiota alters its lipidome and promotes inflammation
| PRJNA783025 | ENA
Project description:Besides promoting inflammation by mobilizing lipid mediators, secreted phospholipase A2 group IIA (sPLA2-IIA) prevents bacterial infection by degrading bacterial membranes. Here we show that despite the restricted intestinal expression of sPLA2-IIA in BALB/c mice, its genetic deletion leads to amelioration of cancer and exacerbation of psoriasis in distal skin. Intestinal expression of sPLA2-IIA is reduced after antibiotics treatment or under germ-free conditions, suggesting its upregulation by gut microbiota. Metagenome, transcriptome and metabolome analyses have revealed that sPLA2-IIA deficiency alters the gut microbiota, accompanied by notable changes in the intestinal expression of genes related to immunity and metabolism as well as the levels of various blood metabolites and fecal bacterial lipids, suggesting that sPLA2-IIA contributes to shaping of the gut microbiota. The skin phenotypes in Pla2g2a–/– mice are lost when they are co-housed with littermate wild-type mice, resulting in mixing of the microbiota between the genotypes, or when they are housed in a more stringent pathogen-free facility, where Pla2g2a expression in wild-type mice is low and the gut microbial compositions in both genotypes are nearly identical. Thus, our results highlight a new aspect of sPLA2-IIA as a modulator of gut microbiota, perturbation of which affects distal skin responses.
2022-01-01 | GSE182283 | GEO
Project description:Streptococcus dysgalactiae subsp. equeisimilis (SDSE) has Lancefield group G or C antigens. Recent epidemiological studies reveal that invasive SDSE infections have been increasing in Asia, Europe and US. Although SDSE possesses similar virulence factors to S. pyogenes including streptolysin S (SLS) and streptolysin O (SLO), some important S. pyogenes virulence factors including active superantigens, SpeB and a hyarulonic acids capsule are missing in SDSE genome. The mechanisms and the key virulence factors for causing invasive diseases by SDSE are poorly understood. Here, we analyzed the transcriptome of SDSE in vivo using the murine sepsis model, revealing the strategy of SDSE to destruct host tissues with the virulence factors and to scavenge depleted nutrients. The expression of SLO operon increased at relatively early stage of infection while the SLS and hyaluronidases upregulated after 4h post infection. Microarray data suggested that SDSE degraded host tissue polysaccharides by streptococcal-secreting poly/oligosaccharide lyases and simultaneously used the Entner-Doudoroff pathway to metabolize acquired carbohydrates. A global negative virulence gene regulator CsrRS of SDSE modulated the expressions of genes encoding SLS and the carbohydrate metabolism enzymes. Moreover, csrS deficient mutant induced sever systemic hemolysis in mice. The most frequently isolated stG6792 strains from invasive disease secreted abundant SLS and SLO rather than other SDSE emm types, indicating the relationship between the SLS and SLO productions and poor outcome by the stG6792 strain infection. Our findings suggest that the concomitant regulation of virulence factors destructing the host tissues and metabolic enzymes play an important role to produce invasive diseases by SDSE.
2013-09-09 | GSE43222 | GEO
Project description:Streptococcus dysgalactiae subsp. equeisimilis (SDSE) has Lancefield group G or C antigens. Recent epidemiological studies reveal that invasive SDSE infections have been increasing in Asia, Europe and US. Although SDSE possesses similar virulence factors to S. pyogenes including streptolysin S (SLS) and streptolysin O (SLO), some important S. pyogenes virulence factors including active superantigens, SpeB and a hyarulonic acids capsule are missing in SDSE genome. The mechanisms and the key virulence factors for causing invasive diseases by SDSE are poorly understood. Here, we analyzed the transcriptome of SDSE in vivo using the murine sepsis model, revealing the strategy of SDSE to destruct host tissues with the virulence factors and to scavenge depleted nutrients. The expression of SLO operon increased at relatively early stage of infection while the SLS and hyaluronidases upregulated after 4h post infection. Microarray data suggested that SDSE degraded host tissue polysaccharides by streptococcal-secreting poly/oligosaccharide lyases and simultaneously used the Entner-Doudoroff pathway to metabolize acquired carbohydrates. A global negative virulence gene regulator CsrRS of SDSE modulated the expressions of genes encoding SLS and the carbohydrate metabolism enzymes. Moreover, csrS deficient mutant induced sever systemic hemolysis in mice. The most frequently isolated stG6792 strains from invasive disease secreted abundant SLS and SLO rather than other SDSE emm types, indicating the relationship between the SLS and SLO productions and poor outcome by the stG6792 strain infection. Our findings suggest that the concomitant regulation of virulence factors destructing the host tissues and metabolic enzymes play an important role to produce invasive diseases by SDSE. To analyze gene expressions in group G streptococci with the murine infection model, we developed a custom microarray for Streptococcus dysgalactiae subsp. equisimilis (SDSE) based on the genome sequences of three SDSE strains; GGS_124, ATCC12923 and RE378. We intraperitoneally inoculated 10^8 CFU of GGS_124 stain and the csrS deficient mutant into ddY mice. Bacterial cells were collected from the abdominal cavity at 0, 2, 4 and 8 h post infection. GGS_124 cells were also collected from OD600=0.6 culture in brain heart infusion broth as a control.
2013-09-09 | E-GEOD-43222 | biostudies-arrayexpress
Project description:The epicardial adipose tissue (EAT) is a visceral adipose tissue in close contact with coronary vessels whose increase is associated with coronary artery disease (CAD). Our goal was to identify candidate molecule(s) characterizing EAT which could intervene in the pathogenesis of CAD. An approach combining microarrays and bioinformatic sequence analysis tools for predicting secreted proteins (TargetP) was applied to paired biopsies of subcutaneous adipose tissue (SAT) and EAT, obtained from patients with or without CAD (NCAD). Results were validated in 3 independent groups of subjects by RT-qPCR, western blot, immuno histochemistry and explants secretion. sPLA2-IIA ranked first among genes coding for potentially secreted proteins with the highest overexpression in EAT in both CAD and NCAD. RT-qPCR confirmed its increased expression in EAT ( p<0.01) and in EAT from CAD as compared to NCAD (49.3 ±13 vs. 17.4 ± 9.7 p<0.01). sPLA2-IIA protein level was higher in EAT than in SAT. EAT explants demonstrated also significantly higher sPLA2-IIA secretion levels than SAT ones (4.37±2.7 vs 0.67± 0.28 ng.ml-1/g tissue/24h,p<0.03). sPLA2-IIA labeling was evidenced in EAT in the stroma vascular fraction between adipocytes and in connective capsules, with no immunostaining of the adipocytes. SAT was weakly labeled following the same pattern. Conclusion: We evidenced for the first time an increased expression of sPLA2-IIA in EAT from patients with CAD, a phospholipase that was shown to be an independent risk factor for CAD. These findings suggest a potentially pathophysiological role of EAT in CAD.
2021-10-20 | GSE18612 | GEO
Project description:<p><strong>AIM:</strong> The role of lipids in periodontitis has not been well studied. Thus, this study aimed to explore periodontitis-associated lipid profile changes and identify differentially expressed lipid metabolites in gingival tissues.</p><p><strong>MATERIALS AND METHODS:</strong> Gingival tissues from 38 patients with periodontitis (periodontitis group) and 38 periodontally healthy individuals (control group) were collected. A UHPLC-QTOF-MS-based non-targeted metabolomics platform was used to identify and compare the lipid profiles of the two groups. The distribution and expression of related proteins were subsequently analyzed via immunohistochemistry to further validate the identified lipids.</p><p><strong>RESULTS:</strong> Lipid profiles significantly differed between the two groups, and 20 differentially expressed lipid species were identified. Lysophosphatidylcholines (lysoPCs), diacylglycerols (DGs) and phosphatidylethanolamines (PEs) were significantly upregulated, while triacylglycerols (TGs) were downregulated in the periodontitis group. Moreover, the staining intensity of ABHD5/CGI-58, secretory phospholipase A2 (sPLA2), and sPLA2-IIA was significantly stronger in the gingival tissues of patients with periodontitis than in those of healthy controls.</p><p><strong>CONCLUSIONS:</strong> LysoPCs, DGs, and PEs were significantly upregulated, whereas TGs were downregulated in gingival tissues of patients with periodontitis. Correspondingly, the immunohistochemical staining of ABHD5/CGI-58, sPLA2 and sPLA2-IIA in gingival tissues was consistent with the downstream production of lipid classes (lysoPCs, TGs and DGs).</p>
2022-08-19 | MTBLS4684 | MetaboLights
Project description:Although some phospholipase A2 forms, the initiator of the arachidonic acid cascade, contribute to carcinogenesis of many organs, the phospholipase A2 group IVc (Pla2g4c) remains to be clarified. When Pla2g4c expression in Rat mammary tumor-1 E4 (RMT-1) cells was knocked down by using specific siRNAs, cell counts were found to decrease to 40 % of the number of control and apoptotic cells were increased. Whole transcript profiling revealed the up-regulation of lipocalin 2 and down-regulation of epithelical marker genes.
2012-04-19 | GSE37351 | GEO
Project description:The bactericidal function of neutrophils are dependent on myriad intrinsic and extrinsic stimuli. Using systems immunology approaches we identified microbiome- and infection-induced changes in neutrophils. We focused on investigating the Prenylcysteine oxidase 1 like (Pcyox1l) protein function. Murine and human Pcyox1l proteins share ninety four percent aminoacid homology revealing significant evolutionary conservation and implicating Pcyox1l in mediating important biological functions. Here we show that the loss of Pcyox1l protein results in significant reductions in the mevalonate pathway impacting autophagy and cellular viability under homeostatic conditions. Concurrently, Pcyox1l CRISPRed-out neutrophils exhibit deficient bactericidal properties. Pcyox1l knock-out mice demonstrate significant susceptibility to infection with the gram-negative pathogen P. aeruginosa exemplified through increased neutrophil infiltrates, hemorrhaging, and reduced bactericidal functionality. Cumulatively, we ascribe a function to Pcyox1l protein as a fundamental regulator of the prenylation pathway and suggest connections beween metabolic responses and neutrophil functionality. Anastasia Petenkova , Shelby A. Auger, Jeffrey Lamb, Daisy Quellier, Cody Carter, On TakTo, Jelena Milosevic, Rana Barghout, Abirami Kugadas, Xiaoxiao Lu, Jennifer Geddes-McAlister, Raina Fichorova, David B. Sykes, Mark D. Distefano, and Mihaela Gadjeva. 2023. Prenylcysteine oxidase 1 like protein is required for neutrophil bactericidal activities. Nat.Comm.
2023-04-14 | PXD031115 | Pride
Project description:Goal of the experiment: To examine differential gene expression in the iliac arteries of cynomolgous monkeys in the presence of small, medium, or large atherosclerotic plaque. Brief description of the experiment: Objective: To examine global gene expression patterns in the iliac arteries of monkeys containing small, medium, or large atherosclerotic plaque. Design: The left iliac artery of 12 ovariectomized cynomolgous monkeys on a high fat diet for 8 years was biopsied. Gene expression was analyzed by DNA microarray and real time RT-PCR. Results: Significant up- or down-regulation of 986 genes was observed in monkey iliac arteries in the presence of atherosclerotic plaque. Changes in gene expression with atherosclerosis ranged from 0.1-151.9-fold. Differentially expressed genes included many cytokines, chemokines, components of signal transduction pathways, and transcriptional activators and repressors, among others. Real time RT-PCR confirmed down-regulation of estrogen receptor 1 (ESR1), claudin 11, BH protocadherin 7 (PCDH7), and the up-regulation of apolipoprotein E (ApoE), growth differentiation factor 15 (GDF15), superoxide dismutase 2 (SOD2), SET domain, bifurcated 2 (SETDB2), phospholipase A2 group IIA (PLA2IIA), phospholipase A2 group VII (PLA2VII), and ring finger protein 149 (RNF149). Conclusions: The gene expression environment in arteries containing atherosclerotic plaque is profoundly different from that of arteries without atherosclerosis. The data suggest that the changes in gene expression contribute to the disease process in diseased arteries.
2011-07-06 | GSE26326 | GEO