{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T14:40:01Z","timestamp":1791384001265,"version":"4.3.3"},"reference-count":94,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"15","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2025,4,11]]},"abstract":"<jats:p>\n                    The enteric pathogen\n                    <jats:italic>Salmonella enterica<\/jats:italic>\n                    serovar Typhimurium relies on the activity of effector proteins to invade, replicate, and disseminate into host epithelial cells and other tissues, thereby causing disease. Secretion and injection of effector proteins into host cells is mediated by dedicated secretion systems, which hence represent major virulence determinants. Here, we report the identification of a synthetic small molecule with drug-like properties, C26, which suppresses the secretion of effector proteins and consequently hinders bacterial invasion of eukaryotic cells. C26 binds to and inhibits HilD, the transcriptional regulator of the major secretion systems. Although sharing the same binding pocket as the previously described long-chain fatty acid ligands, C26 inhibits HilD with a unique binding mode and a distinct mechanism. We provide evidence of intramacrophage activity and present analogs with improved potency and suitability as scaffolds to develop antivirulence agents against\n                    <jats:italic>Salmonella<\/jats:italic>\n                    infections in humans and animals.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.adr5235","type":"journal-article","created":{"date-parts":[[2025,4,11]],"date-time":"2025-04-11T13:59:46Z","timestamp":1744379986000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":5,"title":["Discovery of synthetic small molecules targeting the central regulator of\n                    <i>Salmonella<\/i>\n                    pathogenicity"],"prefix":"10.1126","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0001-7577","authenticated-orcid":true,"given":"Abdelhakim","family":"Boudrioua","sequence":"first","affiliation":[{"name":"Section of Cellular and Molecular Microbiology, Interfaculty 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Germany."},{"name":"German Center for Infection Research (DZIF), partner-site T\u00fcbingen, 72076 T\u00fcbingen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6933-7590","authenticated-orcid":true,"given":"Thales","family":"Kronenberger","sequence":"additional","affiliation":[{"name":"German Center for Infection Research (DZIF), partner-site T\u00fcbingen, 72076 T\u00fcbingen, Germany."},{"name":"Institute of Medical Microbiology and Hygiene, Interfaculty Institute of Microbiology and Infection Medicine (IMIT), University of T\u00fcbingen, Elfriede-Aulhorn-Str. 6, 72076 T\u00fcbingen, Germany."},{"name":"School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, Kuopio 70211, Finland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3970-2483","authenticated-orcid":true,"given":"Vadim S.","family":"Korotkov","sequence":"additional","affiliation":[{"name":"Department of Chemical Biology, Helmholtz Centre for Infection Research (HZI), 38124 Braunschweig, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2990-3660","authenticated-orcid":true,"given":"Wieland","family":"Steinchen","sequence":"additional","affiliation":[{"name":"Center for Synthetic Microbiology, Philipps University of Marburg, Karl-von-Frisch-Str. 14, 35043 Marburg, Germany."},{"name":"Department of Chemistry, Philipps University of Marburg, Hans Meerwein-Str. 4, 35043 Marburg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Kohler","sequence":"additional","affiliation":[{"name":"Section of Cellular and Molecular Microbiology, Interfaculty Institute of Microbiology and Infection Medicine (IMIT), University of T\u00fcbingen, Elfriede-Aulhorn-Str. 6, 72076 T\u00fcbingen, Germany."},{"name":"German Center for Infection Research (DZIF), partner-site T\u00fcbingen, 72076 T\u00fcbingen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-4695-8664","authenticated-orcid":true,"given":"Sophie","family":"Schminke","sequence":"additional","affiliation":[{"name":"Section of Cellular and Molecular Microbiology, Interfaculty Institute of Microbiology and Infection Medicine (IMIT), University of T\u00fcbingen, Elfriede-Aulhorn-Str. 6, 72076 T\u00fcbingen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia-Christina","family":"Schulte","sequence":"additional","affiliation":[{"name":"Section of Cellular and Molecular Microbiology, Interfaculty Institute of Microbiology and Infection Medicine (IMIT), University of T\u00fcbingen, Elfriede-Aulhorn-Str. 6, 72076 T\u00fcbingen, Germany."},{"name":"German Center for Infection Research (DZIF), partner-site T\u00fcbingen, 72076 T\u00fcbingen, 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