Genetic exchange in leishmania is facilitated by IgM natural antibodies.
Ontology highlight
ABSTRACT:
INSTRUMENT(S): LTQ Orbitrap Velos
ORGANISM(S): Leishmania Major Strain Friedlin
SUBMITTER: 
Tiago Serafim
LAB HEAD: Jesus Valenzuela
PROVIDER: PXD038652 | Pride | 2023-08-20
REPOSITORIES: Pride
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| Deamidation__NQ_Sites.txt | Txt | |||
| Oxidation__M_Sites.txt | Txt | |||
| PI22-27419.raw | Raw | |||
| PI22-27420.raw | Raw | |||
| PI22-27421.raw | Raw |
Items per page: 5 1 - 5 of 27 |
Publications
Leishmania genetic exchange is mediated by IgM natural antibodies.
Serafim Tiago D TD Iniguez Eva E Barletta Ana Beatriz F ABF Cecilio Pedro P Doehl Johannes S P JSP Short Mara M Lack Justin J Nair Vinod V Disotuar Maria M Wilson Timothy T Coutinho-Abreu Iliano V IV Meneses Claudio C Andersen John J Alves E Silva Thiago Luiz TL Oliveira Fabiano F Vega-Rodriguez Joel J Barillas-Mury Carolina C Ribeiro José M C JMC Beverley Stephen M SM Kamhawi Shaden S Valenzuela Jesus G JG
Nature 20231025 7985
Host factors that mediate Leishmania genetic exchange are not well defined. Here we demonstrate that natural IgM (IgMn)<sup>1-4</sup> antibodies mediate parasite genetic exchange by inducing the transient formation of a spherical parasite clump that promotes parasite fusion and hybrid formation. We establish that IgMn from Leishmania-free animals binds to the surface of Leishmania parasites to induce significant changes in the expression of parasite transcripts and proteins. Leishmania binding t ...[more]
Similar Datasets
Project description:The alternative sigma factor RpoS plays a central role in the critical host-adaptive response of the Lyme disease spirochete, Borrelia burgdorferi. We previously identified bbd18 as a negative regulator of RpoS but could not inactivate bbd18 in wild-type spirochetes. In the current study we employed an inducible bbd18 gene to demonstrate the essential nature of BBD18 for viability of wild-type spirochete viability in vitro and at a unique point in vivo. Transcriptomic analyses of BBD18 depleted cells demonstrated global induction of RpoS-dependent genes prior to lysis, with the absolute requirement for BBD18, both in vitro and in vivo, circumvented by deletion of rpoS. The increased expression of plasmid prophage genes and the presence of phage particles in the supernatants of lysing cultures indicate that RpoS regulates phage lysis-lysogeny decisions. Through this work we identify a mechanistic link between endogenous transducing prophages and the RpoS-dependent adaptive response of the Lyme disease spirochete. The alternative sigma factor RpoS plays a central role in the critical host-adaptive response of the Lyme disease spirochete, Borrelia burgdorferi. We previously identified bbd18 as a negative regulator of RpoS but could not inactivate bbd18 in wild-type spirochetes. In the current study we employed an inducible bbd18 gene to demonstrate the essential nature of BBD18 for viability of wild-type spirochete viability in vitro and at a unique point in vivo. Transcriptomic analyses of BBD18 depleted cells demonstrated global induction of RpoS-dependent genes prior to lysis, with the absolute requirement for BBD18, both in vitro and in vivo, circumvented by deletion of rpoS. The increased expression of plasmid prophage genes and the presence of phage particles in the supernatants of lysing cultures indicate that RpoS regulates phage lysis-lysogeny decisions. Through this work we identify a mechanistic link between endogenous transducing prophages and the RpoS-dependent adaptive response of the Lyme disease spirochete.
2022-12-12 | PXD037736 | Pride
Project description:Growing evidence suggests the importance of lipid metabolism in pathogenesis of tuberculosis. Neutral lipids form the majority of lipids in caseous granulomas characteristic of tuberculosis. Macrophage lipid droplets form the store house of these lipids, yet infection induced changes in the proteome of these dynamic organelles remains elusive. Here we employed quantitative proteomics to identify alterations induced upon infection with live Mycobacterium tuberculosis in comparison with heat killed bacilli and uninfected macrophages. Association of specific proteins coupled with lysosomal function was found to be increased upon infection with live M. tuberculosis. Biochemical and microscopy based evidence validated the enrichment of the small GTPase Arl8b, the guanine nucleotide effector LAMTOR1, and the scavenger receptor SCARB2 on lipid droplets during live Mtb infection. We validated the localization of Arl8b on lipid droplets using super-resolution microscopy. Increased abundance of these lysosomal proteins on lipid droplets upon infection with live Mtb suggests active manipulation of the host lipid droplets by the pathogen. Furthermore, depletion of lipid droplets upon stable knockdown of diacylglycerol O-acyltransferase led to reduction in lysosomal acidification of infected cells, suggesting an active role of lipid droplets in lysosomal function during infection.
2019-11-14 | PXD008950 | Pride
Project description:Investigation of whole genome expression pattern of 60 and 72 hours post fertilization Danio Rerio embryos exposed to TMT and vehicle control Embryos were exposed to 10uM TMT or control from 48hpf to 60 or 72 hpf. Three replicates were collected for each time point. 40 embryos were pooled to comprise a replicate.
2011-03-23 | E-GEOD-28131 | biostudies-arrayexpress
Project description:The rat pheochromocytoma cell line PC12 cells were cultured in complete DMEM till 80% confluence, then placed at 5000 cells per squared cm. Cells were then plated in 24-well plates for cell viability assay and in T75 flasks for RNA isolation. Medium was replaced with serum-free fresh medium for 12 hours prior to TMT treatment. Gene expression patterns were then analysed using Rat Expression Array 230A Experiment Overall Design: In this study we analize gene expression patterns in PC12 cells treated with Trimethyltin (TMT). We utilized control cells (untreated) and two different concentration (1 and 5) Experiment Overall Design: We used three biological replicates, for the three concentration tested, according to MIAME guidelines Experiment Overall Design: (total 9 chips were used in this study).
2009-04-29 | E-GEOD-5073 | biostudies-arrayexpress
Project description:Smoking is the leading cause of preventable death worldwide. It increases the risk for various diseases including respiratory diseases, vascular diseases and different cancers including lung, oral and bladder cancer. Despite being the leading cause of oral cancer, the molecular mechanisms resulting in malignancy upon cigarette smoke exposure are yet to be fully elucidated. It is crucial to note that disease development is observed upon chronic exposure to cigarette smoke, as opposed to a short-term exposure. Hence, we sought to investigate the effect of chronic smoke exposure on normal oral keratinocytes (OKF6/TERT1). We employed tandem mass tag-based quantitative proteomic and phosphoproteomic approaches to investigate the proteomic and signaling changes in OKF6/TERT1 cells chronically exposed to cigarette smoke compared to untreated cells. LC/MS2 analysis resulted in the quantification of 5,067 proteins among which expression of 360 proteins were found to be dysregulated in at least one replicate. Phosphoproteomic analysis revealed quantification of 3,647 phosphopeptides corresponding to 1,801 proteins. Majority of the dysregulated proteins were seen to be involved in cellular processes such as cell growth, cellular communication and energy metabolism. This study will aid in elucidating the effects of smoking in oral cancer and in the identification of potential candidates molecules which could serve as early detection biomarkers or therapeutic targets.
2018-03-05 | PXD007637 | Pride
Project description:Ayurvedic drug formulations Bacopa monnieri and Centella asiatica are known to have neuroprotective effects. These have been traditionally used in the treatment of Alzhemeir’s disease, and other neurological deficits. Using pan neuronal Aβ42 model of Drosophila melanogaster, a mass spectrometry based quantitative proteomic analysis platform was used to generate the data on proteins altered in response to the Aβ42 toxicity and restoration of altered proteins by consumption of aqueous extracts of two Ayurvedic drug formulations Bacopa monnieri and Centella asiatica aqueous extract. Quantitative proteomic analysis resulted in 0.67 million mass spectra corresponding to 2,59,168 peptide-spectrum matches (PSM) mapping to 24,305 non- redundant peptides corresponding to 11,480 Drosophila melanogaster proteins. Proteins were filtered for >3 PSMs, resulting in 9,540 proteins. Flies expressing Aβ42 significantly altered 517 proteins which were involved in maintaining essential neuronal functions. Supplementing flies with Bacopa monnieri or Centella asiatica extract commonly rescued 224 proteins from Aβ42 toxicity, moreover, extract supplemented group significantly altered proteins which were additionally supporting neuronal maintenance in flies with Aβ42 stress.
2021-11-25 | PXD027101 | Pride
Project description:Eukaryotic genomes are replicated from many origin sites that are licensed by the loading of inactive double hexamers of the replicative DNA helicase, Mcm2-7. How eukaryotic origin positions are specified remains elusive. Here we show that, contrary to the bacterial paradigm, eukaryotic origins are not irrevocably defined by selection of the loading site for the replicative helicase, but can shift in position after helicase loading. Using purified proteins, we show that DNA translocases, including RNA polymerase, can push budding yeast Mcm2-7 double hexamers along DNA. Displaced Mcm2-7 double hexamers support DNA replication initiation distal to the loading site in vitro. In yeast cells that are defective for transcription termination, collisions with RNA polymerase induce a shift in origin positions that correlates with the direction of transcription. These results reveal a eukaryotic origin specification mechanism that departs from the classical replicon model, helping eukaryotic cells to negotiate transcription-replication conflict. 4 samples: one replicate for WT at 37C, two replicates for rat1-1 at 37C, and one replicate for rat1-1 at 24C. All are single-end sequenced via Ion Torrent PGM methodology. rat1 = Nuclear 5' to 3' single-stranded RNA exonuclease; involved in RNA metabolism (http://www.yeastgenome.org/locus/S000005574/overview). 4 ChIP seq samples and their duplicates are submitted. rat1-1 ORC ChIP at 24C and 37C; rat1-1 MCM ChIP at 24C and 37C.
2016-01-07 | E-GEOD-69065 | biostudies-arrayexpress
Project description:Molecular alterations induced by tobacco usage are not well characterized in oral squamous cell carcinoma. Tobacco consumption in chewing or smoking forms is a known risk factor in oral cancer. To understand proteomic changes due to tobacco usage in oral cancer patients we carried out comparative proteomic analysis in oral cancer patients who had history of tobacco using habits (patients who chewed tobacco and patients who smoked tobacco) and those with no history of tobacco consumption. Proteomic analysis resulted in the quantification of 5,848 proteins in smoker cohort, 5,216 in chewer, and 5,320 in non-user cohort. Among these 443, 72 and 139 were significantly dysregulated proteins (p-value≤ 0.05 and 2-fold change) in smoker, chewer and non-user cohorts, respectively. Gene ontology and pathway analysis of significantly dysregulated proteins revealed enrichment of distinct biological processes and pathways in each patient cohort. Proteins associated with collagen formation and antigen processing/presentation pathway were dysregulated in oral cancer patients who smoked tobacco, while keratinization process was enriched in patients who chewed tobacco. We also observed dysregulated proteins in non-users to be involved in ECM proteoglycans, metabolism of carbohydrates and glycosaminoglycans. Immune signaling pathways and muscle contraction were identified as common events dysregulated in all three cohorts. This study helps us to decipher the proteomic alterations induced by tobacco usage in oral cancer patients and will assist in identification of early detection markers to identify high risk population
2022-03-15 | PXD022808 | Pride
Project description:Of the 16 non-structural proteins (Nsps) encoded by SARS CoV-2, Nsp3 is the largest and plays important roles in the viral life cycle. Being a large, multidomain, transmembrane protein, Nsp3 has been the most challenging to characterize. Encoded within the multidomain Nsp3 is the papain-like protease PLpro that cleaves not only the viral protein but also polyubiquitin and the ubiquitin-like modifier ISG15 from host cells. We here compare the interactors of PLpro and Nsp3 and find a largely overlapping interactome. Intriguingly, we find that near full length Nsp3 is a more active protease compared to the minimal PLpro. Using a MALDI-TOF based assay, we screen 7538 approved clinical compounds and identify five compounds that inhibit PLpro. Despite their ability to inhibit PLpro with IC50s in the low micromolar range, the inhibitors do not have any appreciable antiviral activity in cellular SARS-CoV2 infection assays. We therefore engineered nanobodies that bind to the S1 site of PLpro with nanomolar affinity and inhibit the enzyme. Our work highlights the importance of studying Nsp3 and provides tools and valuable insights to investigate Nsp3 biology.
2021-09-15 | PXD022904 | Pride
Project description:The breast cancer incidence has been increasing in China, with the earlier age of onset compared with Western countries. Traditional Chinese medicine has been provided as one of the major source of anti-cancer drugs. Ginseng is one of the most common traditional medicines in China. Ginsenosides, the saponins in the plant Panax (ginseng) are the major active components responsible for their chemopreventive effects from cancer. However, the mechanisms by which ginsenosides exert their anti-cancer effect remain elusive. By combining TMT-based quantitation with TiO2-based phosphopeptide enrichment, we performed a quantitative analysis of the changes of the phosphoproteomes in ginsenoside Rg3-treated breast cancer MDA-MB-231 cells. We were able to quantitate 5,140 phosphorylation sites on 2,041 phosphoproteins. Our data show that the phosphorylation status of 13 sites was changed in MDA-MB-231 cells upon Rg3 treatment. The perturbed phosphoproteins are CPSF7, EEF2, HIRIP3, MAGED2, MPRIP, MYCBP2, PAWR, PPP1R12A, RANBP2, SEPT9, TMPO, and UFL1. These proteins are involved in various biological processes, including protein synthesis, cell division, and inhibition of NF-κB signaling. Our study revealed that Rg3 exerts its anti-cancer effects through a combination of different signaling pathways.
2018-01-08 | PXD003092 | Pride