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Global mapping of Salmonella enterica-host protein-protein interactions during infection

Intracellular bacterial pathogens inject effector proteins to hijack host cellular processes and promote their survival and proliferation. To systematically map effector-host protein-protein interactions (PPIs) during infection, we generated a library of 32 Salmonella enterica serovar Typhimurium (S...

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Main Authors: Walch, Philipp (Author) , Selkrig, Joel (Author) , Knodler, Leigh A. (Author) , Rettel, Mandy (Author) , Stein, Frank (Author) , Fernandez, Keith (Author) , Viéitez, Cristina (Author) , Potel, Clément M. (Author) , Scholzen, Karoline (Author) , Geyer, Matthias (Author) , Rottner, Klemens (Author) , Steele-Mortimer, Olivia (Author) , Savitski, Mikhail M. (Author) , Holden, David W. (Author) , Typas, Athanasios (Author)
Format: Article (Journal)
Language:English
Published: 7 July 2021
In: Cell host and microbe
Year: 2021, Volume: 29, Issue: 8, Pages: 1316-1332.e12
ISSN:1934-6069
DOI:10.1016/j.chom.2021.06.004
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.chom.2021.06.004
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S1931312821002821
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Author Notes:Philipp Walch, Joel Selkrig, Leigh A. Knodler, Mandy Rettel, Frank Stein, Keith Fernandez, Cristina Viéitez, Clément M. Potel, Karoline Scholzen, Matthias Geyer, Klemens Rottner, Olivia Steele-Mortimer, Mikhail M. Savitski, David W. Holden, and Athanasios Typas
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Summary:Intracellular bacterial pathogens inject effector proteins to hijack host cellular processes and promote their survival and proliferation. To systematically map effector-host protein-protein interactions (PPIs) during infection, we generated a library of 32 Salmonella enterica serovar Typhimurium (STm) strains expressing chromosomally encoded affinity-tagged effectors and quantified PPIs in macrophages and epithelial cells. We identified 446 effector-host PPIs, 25 of which were previously described, and validated 13 by reciprocal co-immunoprecipitation. While effectors converged on the same host cellular processes, most had multiple targets, which often differed between cell types. We demonstrate that SseJ, SseL, and SifA modulate cholesterol accumulation at the Salmonella-containing vacuole (SCV) partially via the cholesterol transporter Niemann-Pick C1 protein. PipB recruits the organelle contact site protein PDZD8 to the SCV, and SteC promotes actin bundling by phosphorylating formin-like proteins. This study provides a method for probing host-pathogen PPIs during infection and a resource for interrogating STm effector mechanisms.
Item Description:Gesehen am 14.04.2022
Physical Description:Online Resource
ISSN:1934-6069
DOI:10.1016/j.chom.2021.06.004

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