⮝ Full datasets listing
PXD061863
PXD061863 is an original dataset announced via ProteomeXchange.
Dataset Summary
| Title | Integrative Multi-omics Analysis Reveals CUL4B Regulation of Macrophage Pyroptosis and Innate Defense to Staphylococcus aureus |
| Description | The bacterial pathogen Staphylococcus aureus (SA) causes a broad spectrum of invasive human diseases, exacerbated by acquired antibiotic resistance. Macrophages play a crucial front-line role in innate immunity, significantly influencing SA infection outcomes. Despite progress in understanding SA and macrophage interactions, key questions remain due to the complex and multifaceted interplay of pathogen and host. Using an integrative multi-omics approach and system-level analytics, we focused on the host response in macrophage and SA interactions using a well characterized isolate of community-acquired methicillin-resistant SA (MRSA). These studies identified E3 ubiquitin ligase Cullin 4B (CUL4B) as a key regulatory factor at the nexus of the host innate immune response. We used CRISPR methods to engineer a deletion of CUL4B in the human macrophage cell line THP-1 and subjected WT and mutant macrophages to MRSA challenge. Loss of CUL4B was associated with more rapid intracellular bacterial killing, reduced macrophage cell death, decreased caspase-1 activation, and lower IL-1 beta production, suggesting this E3 ubiquitin ligase played a role in inflammasome activation. In a murine MRSA pneumonia model, CUL4B-deficient mice exhibited enhanced pulmonary bacterial clearance and reduced systemic spread of the pathogen. Whole-lung and serum proteomic profiling revealed increased expression of antimicrobial host proteins and decreased evidence of SA induced inflammatory tissue damage in CUL4B-deficient mice compared to wild-type controls. These findings highlight the role of CUL4B in shaping the host response to MRSA infection, and reveal potential new targets for host-directed therapeutics to improve clinical outcomes for this leading pathogen. |
| HostingRepository | MassIVE |
| AnnounceDate | 2026-09-09 |
| AnnouncementXML | Submission_2026-09-09_14:08:45.449.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Non peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Supported dataset by repository |
| PrimarySubmitter | David Gonzalez |
| SpeciesList | scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606; scientific name: Mus musculus; common name: house mouse; NCBI TaxID: 10090; |
| ModificationList | Phospho; Carbamidomethyl; Oxidation; TMT6plex |
| Instrument | Orbitrap Fusion |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|---|---|---|
| 0 | 2025-03-14 14:07:15 | ID requested | |
| ⏵ 1 | 2026-09-09 14:08:46 | announced |
Publication List
| no publication |
Keyword List
| submitter keyword: Multi-omics, MRSA, Bacterial Pathogen, Proteomics, Staphylococcus aureus, DatasetType:Proteomics |
Contact List
| David J Gonzalez | |
|---|---|
| contact affiliation | UCSD |
| contact email | djgonzalez@health.ucsd.edu |
| lab head | |
| Consuelo Sauceda | |
| contact affiliation | UCSD |
| contact email | csauceda@health.ucsd.edu |
| lab head | |
| Victor Nizet | |
| contact affiliation | University of California, San Diego |
| contact email | vnizet@ucsd.edu |
| lab head | |
| Fatemeh Askarian | |
| contact affiliation | UCSD |
| contact email | faaskarian@health.ucsd.edu |
| lab head | |
| David Gonzalez | |
| contact affiliation | UCSD |
| contact email | gozolabucsd@gmail.com |
| dataset submitter | |
Full Dataset Link List
| MassIVE dataset URI |
| Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://massive-ftp.ucsd.edu/v09/MSV000097334/ |
