{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:57:08Z","timestamp":1760151428159,"version":"build-2065373602"},"reference-count":22,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,3,17]],"date-time":"2022-03-17T00:00:00Z","timestamp":1647475200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AI153202","P20GM130448","P20GM113117","P20GM103638","GM111385"],"award-info":[{"award-number":["AI153202","P20GM130448","P20GM113117","P20GM103638","GM111385"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>We are interested in identifying and characterizing small molecule inhibitors of bacterial virulence factors for their potential use as anti-virulence inhibitors. We identified from high-throughput screening assays a potential activity for avasimibe, a previously characterized acyl-coenzyme A: cholesterol acyltransferase inhibitor, in inhibiting the NleB and SseK arginine glycosyltransferases from Escherichia\u00a0coli and Salmonella enterica, respectively. Avasimibe inhibited the activity of the Citrobacter rodentium NleB, E. coli NleB1, and S. enterica SseK1 enzymes, without affecting the activity of the human serine\/threonine N-acetylglucosamine (O-GlcNAc) transferase. Avasimibe was not toxic to mammalian cells at up to 200 \u00b5M and was neither bacteriostatic nor bactericidal at concentrations of up to 125 \u00b5M. Doses of 10 \u00b5M avasimibe were sufficient to reduce S. enterica abundance in RAW264.7 macrophage-like cells, and intraperitoneal injection of avasimibe significantly reduced C. rodentium survival in mice, regardless of whether the avasimibe was administered pre- or post-infection. We propose that avasimibe or related derivates created using synthetic chemistry may have utility in preventing or treating bacterial infections by inhibiting arginine glycosyltransferases that are important to virulence.<\/jats:p>","DOI":"10.3390\/pathogens11030370","type":"journal-article","created":{"date-parts":[[2022,3,20]],"date-time":"2022-03-20T21:34:27Z","timestamp":1647812067000},"page":"370","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Repurposing Avasimibe to Inhibit Bacterial Glycosyltransferases"],"prefix":"10.3390","volume":"11","author":[{"given":"Md Kamrul","family":"Hasan","sequence":"first","affiliation":[{"name":"College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samir","family":"El Qaidi","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"McDonald","sequence":"additional","affiliation":[{"name":"Infectious Diseases Assay Development\/HTS Laboratory, University of Kansas, Lawrence, KS 66047, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anuradha","family":"Roy","sequence":"additional","affiliation":[{"name":"Infectious Diseases Assay Development\/HTS Laboratory, University of Kansas, Lawrence, KS 66047, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philip R.","family":"Hardwidge","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"11423","DOI":"10.1074\/jbc.M117.790675","article-title":"Nleb\/Ssek Effectors from Citrobacter Rodentium, Escherichia Coli, and Salmonella Enterica Display Distinct Differences in Host Substrate Specificity","volume":"292","author":"Chen","year":"2017","journal-title":"J. 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Commun."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1038\/nature12436","article-title":"Pathogen Blocks Host Death Receptor Signalling by Arginine Glcnacylation of Death Domains","volume":"501","author":"Li","year":"2013","journal-title":"Nature"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1038\/nature12524","article-title":"A Type Iii Effector Antagonizes Death Receptor Signalling During Bacterial Gut Infection","volume":"501","author":"Pearson","year":"2013","journal-title":"Nature"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.chom.2019.06.004","article-title":"Non-Traditional Antibacterial Therapeutic Options and Challenges","volume":"26","author":"Theuretzbacher","year":"2019","journal-title":"Cell Host Microbe"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"435","DOI":"10.3389\/fcimb.2018.00435","article-title":"High-Throughput Screening for Bacterial Glycosyltransferase Inhibitors","volume":"8","author":"Zhu","year":"2018","journal-title":"Front. 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