Structural and biochemical characterization of SrcA, a multi-cargo type III secretion chaperone in Salmonella required for pathogenic association with a host

Cooper, Colin A, Zhang, Kun, Andres, Sara N, Fang, Yuan, Kaniuk, Natalia A, Hannemann, Mandy, Brumell, John H, Foster, Leonard J, Junop, Murray S and Coombes, Brian K (2010) Structural and biochemical characterization of SrcA, a multi-cargo type III secretion chaperone in Salmonella required for pathogenic association with a host. PLoS Pathogens, 6 (2). ISSN 1553-7366

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Abstract

Many Gram-negative bacteria colonize and exploit host niches using a protein apparatus called a type III secretion system (T3SS) that translocates bacterial effector proteins into host cells where their functions are essential for pathogenesis. A suite of T3SS-associated chaperone proteins bind cargo in the bacterial cytosol, establishing protein interaction networks needed for effector translocation into host cells. In Salmonella enterica serovar Typhimurium, a T3SS encoded in a large genomic island (SPI-2) is required for intracellular infection, but the chaperone complement required for effector translocation by this system is not known. Using a reverse genetics approach, we identified a multi-cargo secretion chaperone that is functionally integrated with the SPI-2-encoded T3SS and required for systemic infection in mice. Crystallographic analysis of SrcA at a resolution of 2.5 A revealed a dimer similar to the CesT chaperone from enteropathogenic E. coli but lacking a 17-amino acid extension at the carboxyl terminus. Further biochemical and quantitative proteomics data revealed three protein interactions with SrcA, including two effector cargos (SseL and PipB2) and the type III-associated ATPase, SsaN, that increases the efficiency of effector translocation. Using competitive infections in mice we show that SrcA increases bacterial fitness during host infection, highlighting the in vivo importance of effector chaperones for the SPI-2 T3SS.

Item Type: Article
Additional Information: © 2010 Cooper et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Uncontrolled Keywords: amino acid sequence,animals,bacterial proteins,female,host-parasite interactions,immunoprecipitation,mass spectrometry,mice,mice, inbred c57bl,molecular chaperones,molecular sequence data,protein structure, quaternary,salmonella enterica,sequence homology, amino acid
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
Depositing User: Pure Connector
Date Deposited: 20 Jan 2014 15:59
Last Modified: 21 Apr 2020 22:31
URI: https://ueaeprints.uea.ac.uk/id/eprint/46134
DOI: 10.1371/journal.ppat.1000751

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