{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T00:56:38Z","timestamp":1778806598317,"version":"3.51.4"},"update-to":[{"DOI":"10.1371\/journal.ppat.1009713","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,7,21]],"date-time":"2021-07-21T00:00:00Z","timestamp":1626825600000}}],"reference-count":79,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2021,7,9]],"date-time":"2021-07-09T00:00:00Z","timestamp":1625788800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["1F31AI143147"],"award-info":[{"award-number":["1F31AI143147"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI118903"],"award-info":[{"award-number":["R01AI118903"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R21AI144586"],"award-info":[{"award-number":["R21AI144586"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R01GM136826"],"award-info":[{"award-number":["R01GM136826"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    <jats:italic>Salmonella<\/jats:italic>\n                    hijack host machinery in order to invade cells and establish infection. While considerable work has described the role of host proteins in invasion, much less is known regarding how natural variation in these invasion-associated host proteins affects\n                    <jats:italic>Salmonella<\/jats:italic>\n                    pathogenesis. Here we leveraged a candidate cellular GWAS screen to identify natural genetic variation in the\n                    <jats:italic>ARHGEF26<\/jats:italic>\n                    (\n                    <jats:italic>Rho Guanine Nucleotide Exchange Factor 26<\/jats:italic>\n                    ) gene that renders lymphoblastoid cells susceptible to\n                    <jats:italic>Salmonella<\/jats:italic>\n                    Typhi and Typhimurium invasion. Experimental follow-up redefined ARHGEF26\u2019s role in\n                    <jats:italic>Salmonella<\/jats:italic>\n                    epithelial cell infection. Specifically, we identified complex serovar-by-host interactions whereby ARHGEF26 stimulation of\n                    <jats:italic>S<\/jats:italic>\n                    . Typhi and\n                    <jats:italic>S<\/jats:italic>\n                    . Typhimurium invasion into host cells varied in magnitude and effector-dependence based on host cell type. While ARHGEF26 regulated SopB- and SopE-mediated\n                    <jats:italic>S<\/jats:italic>\n                    . Typhi (but not\n                    <jats:italic>S<\/jats:italic>\n                    . Typhimurium) infection of HeLa cells, the largest effect of ARHGEF26 was observed with\n                    <jats:italic>S<\/jats:italic>\n                    . Typhimurium in polarized MDCK cells through a SopB- and SopE2-independent mechanism. In both cell types, knockdown of the ARHGEF26-associated protein DLG1 resulted in a similar phenotype and serovar specificity. Importantly, we show that ARHGEF26 plays a critical role in\n                    <jats:italic>S<\/jats:italic>\n                    . Typhimurium pathogenesis by contributing to bacterial burden in the enteric fever murine model, as well as inflammation in the colitis infection model. In the enteric fever model, SopB and SopE2 are required for the effects of\n                    <jats:italic>Arhgef26<\/jats:italic>\n                    deletion on bacterial burden, and the impact of\n                    <jats:italic>sopB<\/jats:italic>\n                    and\n                    <jats:italic>sopE2<\/jats:italic>\n                    deletion in turn required ARHGEF26. In contrast, SopB and SopE2 were not required for the impacts of\n                    <jats:italic>Arhgef26<\/jats:italic>\n                    deletion on colitis. A role for ARHGEF26 on inflammation was also seen in cells, as knockdown reduced IL-8 production in HeLa cells. Together, these data reveal pleiotropic roles for ARHGEF26 during infection and highlight that many of the interactions that occur during infection that are thought to be well understood likely have underappreciated complexity.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1009713","type":"journal-article","created":{"date-parts":[[2021,7,9]],"date-time":"2021-07-09T14:29:43Z","timestamp":1625840983000},"page":"e1009713","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":14,"title":["ARHGEF26 enhances Salmonella invasion and inflammation in cells and mice"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9037-8418","authenticated-orcid":true,"given":"Jeffrey S.","family":"Bourgeois","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liuyang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7630-6231","authenticated-orcid":true,"given":"Agustin F.","family":"Rabino","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0273-6284","authenticated-orcid":true,"given":"Jeffrey","family":"Everitt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monica I.","family":"Alvarez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4082-6985","authenticated-orcid":true,"given":"Sahezeel","family":"Awadia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3177-6808","authenticated-orcid":true,"given":"Erika S.","family":"Wittchen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7116-4411","authenticated-orcid":true,"given":"Rafael","family":"Garcia-Mata","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0113-5981","authenticated-orcid":true,"given":"Dennis C.","family":"Ko","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2021,7,9]]},"reference":[{"issue":"3","key":"ppat.1009713.ref001","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1084\/jem.31.3.293","article-title":"The Ormation of Vacuoles Due to Bacillus Typhosus in the Cells of Tissue Cultures of the Intestine of the Chick Embryo","volume":"31","author":"MR Lewis","year":"1920","journal-title":"J Exp Med"},{"key":"ppat.1009713.ref002","unstructured":"Salmonella interactions with host cells: type III secretion at work., (2001)."},{"key":"ppat.1009713.ref003","unstructured":"Cloning and molecular characterization of genes whose products allow Salmonella typhimurium to penetrate tissue culture cells., (1989)."},{"issue":"5","key":"ppat.1009713.ref004","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1016\/S0092-8674(00)81442-7","article-title":"S. typhimurium encodes an 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