PXD018740

PXD018740 is an original dataset announced via ProteomeXchange.

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

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.

Dataset with its publication pending

submitter keyword: MS-MS, TMT, mouse,Citrobacter rodentium

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

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PRIDE project URI

• PRIDE
  1. PXD018740
     1. Label: PRIDE project
     2. Name: Deconstructing a type III secretion system effector network unravels the inherent robustness and plasticity in pathogenesis and immunity