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Here, we used a proteomic approach to characterize the secretome of a clinical strain of invasive non-typhoidal\n              <jats:italic>Salmonella enterica<\/jats:italic>\n              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.\n              <jats:italic>sseM<\/jats:italic>\n              is widely distributed among the five subspecies of\n              <jats:italic>Salmonella enterica,<\/jats:italic>\n              is found in many clinically relevant serovars, and is co-transcribed with\n              <jats:italic>pipB2<\/jats:italic>\n              , a SPI-2 effector gene. The 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, \u03b2-2-syntrophin, utrophin\/dystrophin, \u03b1-catulin, \u03b1-dystrobrevin, and \u03b2-dystrobrevin. The interaction between SseM and \u03b2-2-syntrophin and \u03b1-dystrobrevin was verified in\n              <jats:italic>Salmonella<\/jats:italic>\n              Typhimurium-infected cells and relied on the postsynaptic density-95\/discs large\/zonula occludens-1 (PDZ) domain of \u03b2-2-syntrophin and a sequence corresponding to a PDZ-binding motif (PBM) in SseM. A \u0394\n              <jats:italic>sseM<\/jats:italic>\n              mutant strain had a small competitive advantage over the wild-type strain in the\n              <jats:italic>S<\/jats:italic>\n              . Typhimurium\/mouse model of systemic disease. This phenotype was complemented by a plasmid expressing wild-type SseM from\n              <jats:italic>S<\/jats:italic>\n              . Typhimurium or\n              <jats:italic>S<\/jats:italic>\n              . Enteritidis and was dependent on the PBM of SseM. Therefore, a PBM within a\n              <jats:italic>Salmonella<\/jats:italic>\n              effector mediates interactions with the DAPC and modulates the systemic growth of bacteria in mice. Furthermore, the \u0394\n              <jats:italic>sseM<\/jats:italic>\n              mutant strain displayed enhanced replication in bone marrow-derived macrophages, demonstrating that SseM restrains intracellular bacterial growth to modulate\n              <jats:italic>Salmonella<\/jats:italic>\n              virulence.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>IMPORTANCE<\/jats:title>\n            <jats:p>\n              In\n              <jats:italic>Salmonella enterica<\/jats:italic>\n              , the injectisome machinery encoded by\n              <jats:italic>Salmonella<\/jats:italic>\n              pathogenicity island 2 (SPI-2) is conserved among the five subspecies and delivers proteins (effectors) into host cells, which are required for\n              <jats:italic>Salmonella<\/jats:italic>\n              virulence. The identification and functional characterization of SPI-2 injectisome effectors advance our understanding of the interplay between\n              <jats:italic>Salmonella<\/jats:italic>\n              and its host(s). Using an optimized method for preparing secreted proteins and a clinical isolate of the invasive non-typhoidal\n              <jats:italic>Salmonella enterica<\/jats:italic>\n              serovar Enteritidis strain D24359, we identified 22 known SPI-2 injectisome effectors and one new effector\u2014SseM. SseM modulates bacterial growth during murine infection and has a sequence corresponding to a postsynaptic density-95\/discs large\/zonula occludens-1 (PDZ)-binding motif that is essential for interaction with the PDZ-containing host protein \u03b2-2-syntrophin and other components of the dystrophin-associated protein complex (DAPC). To our knowledge, SseM is unique among\n              <jats:italic>Salmonella<\/jats:italic>\n              effectors in containing a functional PDZ-binding motif and is the first bacterial protein to target the DAPC.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/mbio.01128-24","type":"journal-article","created":{"date-parts":[[2024,6,21]],"date-time":"2024-06-21T13:00:37Z","timestamp":1718974837000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":9,"title":["Modulation of\n            <i>Salmonella<\/i>\n            virulence by a novel SPI-2 injectisome effector that interacts with the dystrophin-associated protein complex"],"prefix":"10.1128","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3340-4090","authenticated-orcid":false,"given":"Xiu-Jun","family":"Yu","sequence":"first","affiliation":[{"name":"Department of Infectious Disease, Centre for Bacterial Resistance Biology, Imperial College London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5727-5545","authenticated-orcid":true,"given":"Haixia","family":"Xie","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, Hubei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease, Centre for Bacterial Resistance Biology, Imperial College London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruhong","family":"Hou","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease, Centre for Bacterial Resistance Biology, Imperial College London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander V.","family":"Predeus","sequence":"additional","affiliation":[{"name":"Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Blanca M.","family":"Perez Sepulveda","sequence":"additional","affiliation":[{"name":"Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jay C. 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