{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T04:52:37Z","timestamp":1784177557848,"version":"3.55.0"},"reference-count":56,"publisher":"American Society for Microbiology","issue":"3","license":[{"start":{"date-parts":[[2024,3,6]],"date-time":"2024-03-06T00:00:00Z","timestamp":1709683200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/doi.org\/10.1128\/ASMCopyrightv2"},{"start":{"date-parts":[[2024,3,6]],"date-time":"2024-03-06T00:00:00Z","timestamp":1709683200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"U.S. Department of Defense","award":["W81XWH-20-1-0296"],"award-info":[{"award-number":["W81XWH-20-1-0296"]}]},{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["5T32AI055449"],"award-info":[{"award-number":["5T32AI055449"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2024,3,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              <jats:italic>Clostridioides difficile<\/jats:italic>\n              infection (CDI) is a leading cause of hospital-acquired diarrhea, which often stems from disruption of the gut microbiota by broad-spectrum antibiotics. The increasing prevalence of antibiotic-resistant\n              <jats:italic>C. difficile<\/jats:italic>\n              strains, combined with disappointing clinical trial results for recent antibiotic candidates, underscores the urgent need for novel CDI antibiotics. To this end, we investigated\n              <jats:italic>C. difficile<\/jats:italic>\n              enoyl ACP reductase (\n              <jats:italic>Cd<\/jats:italic>\n              FabK), a crucial enzyme in\n              <jats:italic>de novo<\/jats:italic>\n              fatty acid synthesis, as a drug target for microbiome-sparing antibiotics. To test this concept, we evaluated the efficacy and\n              <jats:italic>in vivo<\/jats:italic>\n              spectrum of activity of the phenylimidazole analog 296, which is validated to inhibit intracellular\n              <jats:italic>Cd<\/jats:italic>\n              FabK. Against major CDI-associated ribotypes 296 had an Minimum inhibitory concentration (MIC\n              <jats:sub>90<\/jats:sub>\n              ) of 2 \u00b5g\/mL, which was comparable to vancomycin (1 \u00b5g\/mL), a standard of care antibiotic. In addition, 296 achieved high colonic concentrations and displayed dosed-dependent efficacy in mice with colitis CDI. Mice that were given 296 retained colonization resistance to\n              <jats:italic>C. difficile<\/jats:italic>\n              and had microbiomes that resembled the untreated mice. Conversely, both vancomycin and fidaxomicin induced significant changes to mice microbiomes, in a manner consistent with prior reports.\n              <jats:italic>Cd<\/jats:italic>\n              FabK, therefore, represents a potential target for microbiome-sparing CDI antibiotics, with phenylimidazoles providing a good chemical starting point for designing such agents.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/aac.01222-23","type":"journal-article","created":{"date-parts":[[2024,1,24]],"date-time":"2024-01-24T14:00:14Z","timestamp":1706104814000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":4,"title":["<i>In vivo<\/i>\n            evaluation of\n            <i>Clostridioides difficile<\/i>\n            enoyl-ACP reductase II (FabK) inhibition by phenylimidazole unveils a promising narrow-spectrum antimicrobial strategy"],"prefix":"10.1128","volume":"68","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-8884-1298","authenticated-orcid":false,"given":"Chetna","family":"Dureja","sequence":"first","affiliation":[{"name":"Center for Infectious and Inflammatory Diseases, Institute of Biosciences and Technology, Texas A&amp;M Health Science Center, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob T.","family":"Rutherford","sequence":"additional","affiliation":[{"name":"Center for Infectious and Inflammatory Diseases, Institute of Biosciences and Technology, Texas A&amp;M Health Science Center, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fahad B.A.","family":"Pavel","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, Memphis, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krissada","family":"Norseeda","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, The Daniel K. Inouye College of Pharmacy, University of Hawaii at Hilo, Hilo, Hawaii, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isaac","family":"Prah","sequence":"additional","affiliation":[{"name":"Center for Infectious and Inflammatory Diseases, Institute of Biosciences and Technology, Texas A&amp;M Health Science Center, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dianqing","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, The Daniel K. Inouye College of Pharmacy, University of Hawaii at Hilo, Hilo, Hawaii, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirk E.","family":"Hevener","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, Memphis, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2214-8105","authenticated-orcid":false,"given":"Julian G.","family":"Hurdle","sequence":"additional","affiliation":[{"name":"Center for Infectious and Inflammatory Diseases, Institute of Biosciences and Technology, Texas A&amp;M Health Science Center, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1910215"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhin.2008.08.012"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cis356"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cis462"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jiac.2019.12.020"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02112-17"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiv256"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkad194"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofab365"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2020.10.046"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofw275"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(18)30614-5"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1602615"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-022-01805-0"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2106516"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbalip.2016.09.014"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-009-8704-7"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1021\/ar700156e"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01741-15"},{"key":"e_1_3_4_21_2","first-page":"146","article-title":"Fatty acid biosynthesis as a target for novel antibacterials","volume":"5","author":"Heath RJ","year":"2004","unstructured":"Heath RJ, Rock CO. 2004. 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