PXD018740 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Deconstructing a type III secretion system effector network unravels the inherent robustness and plasticity in pathogenesis and immunity |
Description | Many Gram-negative pathogens use type III secretion systems to inject networks of effectors that subvert host cell processes. We modelled the robustness of such network using the mouse pathogen Citrobacter rodentium (encoding 31 effectors) through sequential deletions of effector genes, generating 100 distinct mutant combinations, which were tested in vivo. Counterintuitively, mutants lacking 19 unrelated effectors (CR14) or 10 immune-modulating effectors (CRi9) colonised and induced conserved molecular signatures of infection in intestinal epithelial cells. Specifically, CRi9 triggered heightened colonic secretion of TNF, IL-22, IL-17A and IFN-γ, while CR14 induced high-level secretion of IL-6 and GM-CSF with lower recruitment of myeloid cells. Yet, both CR14 and CRi9 induced sterile immunity. A machine learning model, trained on the mutant phenotypes and effector function, predicted an unprecedented combination of colonisation-failure effector mutations, which was validated experimentally. These results reveal the robustness and combinatorial plasticity of both the effector network and host immunity. |
HostingRepository | PRIDE |
AnnounceDate | 2024-10-22 |
AnnouncementXML | Submission_2024-10-22_05:37:20.430.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | James Wright |
SpeciesList | scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; scientific name: Citrobacter rodentium; NCBI TaxID: 67825; |
ModificationList | TMT6plex-126 reporter+balance reagent acylated residue; monohydroxylated residue; iodoacetamide derivatized residue; deamidated residue |
Instrument | Orbitrap Fusion |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2020-04-22 15:21:42 | ID requested | |
1 | 2022-05-31 05:53:39 | announced | |
⏵ 2 | 2024-10-22 05:37:20 | announced | 2024-10-22: Updated project metadata. |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: MS-MS, TMT, mouse,Citrobacter rodentium |
Contact List
Jyoti Choudhary |
contact affiliation | The Institute of Cancer Research, London |
contact email | jyoti.choudhary@icr.ac.uk |
lab head | |
James Wright |
contact affiliation | The Institute of Cancer Research |
contact email | james.wright@icr.ac.uk |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD018740
- Label: PRIDE project
- Name: Deconstructing a type III secretion system effector network unravels the inherent robustness and plasticity in pathogenesis and immunity