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Typhimurium activates Rho family GTPases, primarily CDC42, to modulate the actin cytoskeletal network for invasion. The host intracellular protein network that engages CDC42 and influences the pathogen's invasive capacity are relatively unclear. Here, proteomic analyses of canonical and variant CDC42 interactomes identified a poorly characterized CDC42 interacting protein, CDC42EP1, whose intracellular localization is rapidly redistributed and aggregated around the invading bacteria. CDC42EP1 associates with SEPTIN\u20107 and Villin, and its relocalization and bacterial engagement depend on host CDC42 and <jats:italic>S<\/jats:italic>. Typhimurium's capability of activating CDC42. Unlike CDC42, CDC42EP1 is not required for <jats:italic>S<\/jats:italic>. Typhimurium's initial cellular entry but is found to associate with <jats:italic>Salmonella<\/jats:italic>\u2010containing vacuoles after long\u2010term infections, indicating a contribution to the pathogen's intracellular growth and replication. These results uncover a new host regulator of enteric <jats:italic>Salmonella<\/jats:italic> infections, which may be targeted to restrict bacterial load at the primary site of infection to prevent systemic spread.<\/jats:p>","DOI":"10.1002\/jcp.31142","type":"journal-article","created":{"date-parts":[[2023,10,25]],"date-time":"2023-10-25T12:16:08Z","timestamp":1698236168000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Salmonella engages CDC42 effector protein 1 for intracellular invasion"],"prefix":"10.1002","volume":"239","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1827-9324","authenticated-orcid":false,"given":"Sheila","family":"Bandyopadhyay","sequence":"first","affiliation":[{"name":"Department of Biological Sciences Rutgers University Newark New Jersey 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