Global Mapping of Salmonella Enterica-host Protein-protein Interactions During Infection

Overview

Journal Cell Host Microbe

Publisher Cell Press

Specialties Infectious Diseases
Microbiology

Date 2021 Jul 8

PMID 34237247

Citations 33

Authors

Philipp Walch

Joel Selkrig

Leigh A Knodler

Mandy Rettel

Frank Stein

Keith Fernandez

Cristina Vieitez

Clement M Potel

Karoline Scholzen

Matthias Geyer

Klemens Rottner

Olivia Steele-Mortimer

Mikhail M Savitski

David W Holden

Athanasios Typas

Affiliations

Soon will be listed here.

Abstract

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.

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