PXD018375-1

PXD018375 is an original dataset announced via ProteomeXchange.

Title	Global mapping of Salmonella enterica-host protein-protein interactions during infection
Description	Intracellular bacterial pathogens inject a cocktail of effector proteins into host cells to hijack diverse cellular processes and promote their survival and proliferation. Salmonella enterica serovar Typhimurium (STm) uses two Type 3 secretion system (T3SS) to deliver a suite of effector proteins into host cells, however, knowledge of their host-targets remains sparse. To systematically map STm effector-host protein-protein interactions (PPIs) during active infection, we generated a library of 32 STm strains expressing affinity-tagged effector proteins from their endogenous chromosomal loci. Tagged-effector strains were then used to infect macrophages or epithelial cells, and PPIs were detected by Affinity-Purification Quantitative Mass-Spectrometry (AP-QMS) under both native and cross-linking conditions. We recovered 25 previously described effector-host PPIs, along with 421 novel interactions across the two cell lines tested, as well as several effector-effector PPIs. While effectors converged on specific host cellular processes, which varied across cell types, most had multiple host targets. Using reciprocal co-immunoprecipitations, we could validated 13 out of 22 new PPIs, demonstrating an accuracy of at least 59% for the AP-QMS approach. To illustrate the utility of this resource for discovering novel infection biology, we first showed that SseJ and SseL cooperate to control cholesterol transport at the Salmonella Containing Vacuole (SCV) via the Niemann-Pick C1 protein (NPC1). Second, we uncovered that PipB directly binds and recruits the organelle contact site protein PDZD8 to the SCV. Third, we elucidated a novel mechanism whereby the effector kinase SteC promotes host actin bundling, by directly interacting and phosphorylating formin-like proteins. Overall, we provide a systems-wide host-bacterial pathogen physical interactome resource, to our knowledge the first in an infection context, with broad implications for effector function and cooperation.
HostingRepository	PRIDE
AnnounceDate	2021-06-25
AnnouncementXML	Submission_2021-06-25_00:22:36.796.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Frank Stein
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2020-04-04 16:00:46	ID requested
⏵ 1	2021-06-25 00:22:37	announced

Dataset with its publication pending

submitter keyword: AP/MS, Salmonella, bacterial pathogen, effectors

Dr. Athanasios Typas
contact affiliation	European Molecular Biology Laboratory (EMBL), Genome Biology Unit, Meyerhofstrasse 1, 69117 Heidelberg, Germany
contact email	typas@embl.de
lab head
Frank Stein
contact affiliation	EMBL
contact email	frank.stein@embl.de
dataset submitter

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://ftp.pride.ebi.ac.uk/pride/data/archive/2021/06/PXD018375

PRIDE project URI

• PRIDE
  1. PXD018375
     1. Label: PRIDE project
     2. Name: Global mapping of Salmonella enterica-host protein-protein interactions during infection