| Title: |
Modulation of Salmonella virulence by a novel SPI-2 injectisome effector that interacts with the dystrophin-associated protein complex |
| Authors: |
Yu, X-J; Xie, H; Li, Y; Liu, M; Hou, R; Predeus, AV; Perez Sepulveda, BM; Hinton, JCD; Holden, DW; Thurston, T |
| Publisher Information: |
American Society for Microbiology |
| Publication Year: |
2024 |
| Collection: |
Imperial College London: Spiral |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| Language: |
unknown |
| Relation: |
mBio; http://hdl.handle.net/10044/1/112409 |
| DOI: |
10.1128/mbio.01128-24 |
| Availability: |
http://hdl.handle.net/10044/1/112409; https://doi.org/10.1128/mbio.01128-24 |
| Rights: |
Copyright © 2024 Yu et al. This is an open-accessarticle distributed under the terms of the CreativeCommons Attribution 4.0 International license. ; https://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.6F44B988 |
| Database: |
BASE |