{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T23:35:55Z","timestamp":1792798555194,"version":"4.5.0"},"reference-count":31,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2025,4,2]],"date-time":"2025-04-02T00:00:00Z","timestamp":1743552000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,4,2]],"date-time":"2025-04-02T00:00:00Z","timestamp":1743552000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"Acurx Pharmaceuticals, Inc"},{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["R01AI139261"],"award-info":[{"award-number":["R01AI139261"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"name":"HHS | NIH | National Cancer Institute","award":["R01CA215784"],"award-info":[{"award-number":["R01CA215784"]}]},{"name":"HHS | NIH | National Center for Advancing Translational Sciences","award":["5TL1TR002318-08"],"award-info":[{"award-number":["5TL1TR002318-08"]}],"id":[{"id":"https:\/\/ror.org\/04pw6fb54","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2025,4,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Ibezapolstat (IBZ) is a competitive inhibitor of the bacterial Pol IIIC enzyme in clinical development for the treatment of\n                      <jats:italic>Clostridioides difficile<\/jats:italic>\n                      infection (CDI). Previous studies demonstrated that IBZ carries a favorable microbiome diversity profile compared to vancomycin (VAN). However, head-to-head comparisons with other CDI antibiotics have not been done. The purpose of this study was to compare microbiome changes associated with IBZ to other clinically used CDI antibiotics. Groups of germ-free (GF) mice received a fecal microbiota transplant from one of two healthy human donors and were subsequently exposed to either IBZ, VAN, fidaxomicin (FDX), metronidazole (MET), or no antibiotic (control). 16S rRNA encoding gene sequencing of temporally collected stool samples was used to compare the gut microbiome perturbations between treatment and no-drug control groups. Among the tested antibiotics, the most significant change in microbiome diversity was observed in MET-treated mice. Each antibiotic had a unique effect, but changes in alpha and beta diversities following FDX- and IBZ-treated groups were less pronounced than those observed in VAN- or MET-treated groups. By the end of therapy, both IBZ and FDZ increased the relative abundance of\n                      <jats:italic>Bacteroidota<\/jats:italic>\n                      (phylum), with IBZ additionally increasing the relative abundance of\n                      <jats:italic>Actinomycetota<\/jats:italic>\n                      (phylum). In microbiome-humanized mice, IBZ and FDX had smaller effects on gut microbiome diversity than VAN and MET. Notable differences were observed between the microbiome of IBZ- and FDX-treated groups, which may allow for differentiation of these two antibiotics in future studies.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/aac.01604-24","type":"journal-article","created":{"date-parts":[[2025,2,25]],"date-time":"2025-02-25T09:13:06Z","timestamp":1740474786000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":10,"title":["The impact of ibezapolstat and other\n                    <i>Clostridioides difficile<\/i>\n                    infection-relevant antibiotics on the microbiome of humanized mice"],"prefix":"10.1128","volume":"69","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-8289-5970","authenticated-orcid":true,"given":"Trenton M.","family":"Wolfe","sequence":"first","affiliation":[{"name":"Department of Microbiology and Cell Biology, Montana State University","place":["Bozeman, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4772-188X","authenticated-orcid":true,"given":"Jinhee","family":"Jo","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice and Translational Research, University of Houston College of Pharmacy","place":["Houston, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nick V.","family":"Pinkham","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Cell Biology, Montana State University","place":["Bozeman, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2063-7503","authenticated-orcid":true,"given":"Kevin W.","family":"Garey","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice and Translational Research, University of Houston College of Pharmacy","place":["Houston, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6891-8537","authenticated-orcid":true,"given":"Seth T.","family":"Walk","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Cell Biology, Montana State University","place":["Bozeman, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1910215"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2014.01.059"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.00970-22"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciab549"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-117-4-297"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-04545-z"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkw383"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-39429-x"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/spectrum.01904-21"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciac096"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.2174\/157340811798807597"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkt900"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkaa364"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/aac.02244-21"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-07803-9"},{"key":"e_1_3_5_17_2","first-page":"488","article-title":"Effects of the physical form of the diet on food intake, growth, and body composition changes in mice","volume":"50","author":"Yan L","year":"2011","unstructured":"Yan L, Combs GF, DeMars LC, Johnson LK. 2011. 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U.S. Dept. of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research, Rockville, MD."},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.01043-13"},{"key":"e_1_3_5_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.01541-09"},{"key":"e_1_3_5_22_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btr381"},{"key":"e_1_3_5_23_2","doi-asserted-by":"publisher","DOI":"10.7717\/peerj.1487"},{"key":"e_1_3_5_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.00062-07"},{"key":"e_1_3_5_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.anaerobe.2016.05.003"},{"key":"e_1_3_5_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-022-01964-3"},{"key":"e_1_3_5_27_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-017-1175-y"},{"key":"e_1_3_5_28_2","doi-asserted-by":"publisher","DOI":"10.3390\/microorganisms7010014"},{"key":"e_1_3_5_29_2","doi-asserted-by":"publisher","DOI":"10.1136\/gut.27.10.1169"},{"key":"e_1_3_5_30_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0076269"},{"key":"e_1_3_5_31_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkm113"},{"key":"e_1_3_5_32_2","doi-asserted-by":"publisher","DOI":"10.3109\/00498257509052069"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.01604-24","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.01604-24","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,4]],"date-time":"2025-04-04T01:37:44Z","timestamp":1743730664000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/aac.01604-24"}},"subtitle":[],"editor":[{"given":"Anne-Catrin","family":"Uhlemann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,4,2]]},"references-count":31,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025,4,2]]}},"alternative-id":["10.1128\/aac.01604-24"],"URL":"https:\/\/doi.org\/10.1128\/aac.01604-24","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,2]]},"assertion":[{"value":"2024-11-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-01-29","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-02-25","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e01604-24"}}