Modulation of Salmonella virulence by a novel SPI-2 injectisome effector that interacts with the dystrophin-associated protein complex
Author(s)
Type
Journal Article
Abstract
The injectisome encoded by Salmonella pathogenicity island 2 (SPI-2) had been thought to translocate 28 effectors. Here, we used a proteomic approach to characterise the secretome of a clinical strain of invasive non-typhoidal Salmonella enterica serovar Enteritidis, that had been mutated to cause hyper-secretion of the SPI-2 injectisome effectors. Along with many known effectors, we discovered the novel SseM protein. sseM is widely distributed between the five subspecies of Salmonella enterica, is found in many clinically-relevant serovars, and is co-transcribed with pipB2, a SPI-2 effector gene. Translocation of SseM required a functional SPI-2 injectisome. Following expression in human cells, SseM interacted with five components of the dystrophin-associated protein complex (DAPC), namely -2-syntrophin, utrophin/ dystrophin, -catulin, -dystrobrevin and -dystrobrevin. The interaction between SseM and -2-syntrophin and -dystrobrevin was verified in S. Typhimurium-infected cells and relied on the PDZ domain of -2-syntrophin and a sequence corresponding to a PDZ-binding motif (PBM) in SseM. A sseM mutant strain had a small competitive advantage over the wild-type strain in the S. Typhimurium/mouse model of systemic disease. This phenotype was complemented by a plasmid expressing wild type SseM from S. Typhimurium or S. Enteritidis and was dependent on the PBM of SseM. Therefore, a PBM within a Salmonella effector mediates interactions with the DAPC and modulates systemic growth of bacteria in mice. Furthermore, the sseM mutant strain displayed enhanced replication in bone marrow-derived macrophages, demonstrating that SseM restrains intracellular bacterial growth to modulate Salmonella virulence.
Date Issued
2024-07
Date Acceptance
2024-05-16
Citation
mBio, 2024, 15 (7)
ISSN
2150-7511
Publisher
American Society for Microbiology
Journal / Book Title
mBio
Volume
15
Issue
7
Copyright Statement
Copyright © 2024 Yu et al. This is an open-accessarticle distributed under the terms of the CreativeCommons Attribution 4.0 International license.
License URL
Identifier
https://www.sciencedirect.com/org/science/article/pii/S2150751124003307
Publication Status
Published
Date Publish Online
2024-06-21