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PXD060632

PXD060632 is an original dataset announced via ProteomeXchange.

Dataset Summary
Title¬Helicobacter pylori CagA and Cag type IV secretion system activity have key roles in triggering gastric transcriptional and proteomic alterations
DescriptionColonization of the human stomach with cag pathogenicity island (PAI)-positive H. pylori strains is associated with increased gastric cancer risk compared to colonization with cag PAI-negative strains. To evaluate the contributions of the Cag type IV secretion system (T4SS) and CagA (a secreted bacterial oncoprotein) to gastric molecular alterations relevant for carcinogenesis, we infected Mongolian gerbils with a Cag T4SS-positive wild-type (WT) H. pylori strain, one of two Cag T4SS mutant strains (∆cagT or ∆cagY), or a ∆cagA mutant for 12 weeks. Histologic staining revealed a biphasic distribution of gastric inflammation severity (either minimal or severe) in WT-infected animals and minimal inflammation in mutant-infected animals. Atrophic gastritis (a premalignant condition), dysplasia, and gastric adenocarcinoma were only detected in WT-infected animals with high inflammation scores. Transcriptional profiling and analyses of micro-extracted tryptic peptides (LC-MS/MS and imaging mass spectrometry) revealed more than a thousand molecular alterations in gastric tissues from WT-infected animals with high inflammation scores compared to uninfected tissues and few alterations in tissues from other groups of infected animals. Proteins with altered abundance in animals with severe Cag T4SS-induced inflammation mapped to multiple pathways, including the complement/coagulation cascade and proteasome pathway. Proteins exhibiting markedly increased abundance in tissues from H. pylori-infected animals with severe inflammation included calprotectin components, lysozyme, lactoferrin, superoxide dismutase, eosinophil peroxidase, proteins involved in proteasome activation, STAT1, TrpRS, GBP2, and IIGP1. These results demonstrate key roles for CagA and Cag T4SS activity in promoting gastric mucosal inflammation, transcriptional alterations, and proteomic alterations relevant to gastric carcinogenesis.
HostingRepositoryPRIDE
AnnounceDate2025-02-28
AnnouncementXMLSubmission_2025-02-27_20:03:55.745.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterHayes McDonald
SpeciesList scientific name: Meriones unguiculatus; NCBI TaxID: 10047;
ModificationListNo PTMs are included in the dataset
InstrumenttimsTOF HT
Dataset History
RevisionDatetimeStatusChangeLog Entry
02025-02-10 08:12:28ID requested
12025-02-27 20:03:56announced
Publication List
10.1128/IAI.00595-24;
Keyword List
submitter keyword: Helicobacter pylori, inflammation, gastric cancer, carcinogenesis
Contact List
Timothy L. Cover
contact affiliationVanderbilt University departments of Medicine and Pathology, Microbiology, and Immunology
contact emailtimothy.l.cover@vumc.org
lab head
Hayes McDonald
contact affiliationVanderbilt University
contact emailhayes.mcdonald@vanderbilt.edu
dataset submitter
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Dataset FTP location
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