{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T19:53:36Z","timestamp":1789674816866,"version":"4.0.1"},"reference-count":58,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2024,10,8]],"date-time":"2024-10-08T00:00:00Z","timestamp":1728345600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/doi.org\/10.1128\/ASMCopyrightv2"},{"start":{"date-parts":[[2024,10,8]],"date-time":"2024-10-08T00:00:00Z","timestamp":1728345600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"HHS | National Institutes of Health","award":["R01AI136904, R01AI167284"],"award-info":[{"award-number":["R01AI136904, R01AI167284"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2024,10,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              Antimicrobial resistance (AMR) has led to a marked reduction in the effectiveness of many antibiotics, representing a substantial and escalating concern for global health. Particularly alarming is resistance in Gram-negative bacteria due to the scarcity of therapeutic options for treating infections caused by these pathogens. This challenge is further compounded by the rising incidence of resistance to colistin, an antibiotic traditionally considered a last resort for the treatment of multi-drug resistant (MDR) Gram-negative bacterial infections. In this study, we demonstrate that adjuvants restore colistin sensitivity\n              <jats:italic>in vivo<\/jats:italic>\n              . We previously reported that the salicylanilide kinase inhibitor IMD-0354, which was originally developed to inhibit the human kinase IKK\u03b2 in the NF\u03baB pathway, is a potent colistin adjuvant. Subsequent analog synthesis using an amide isostere approach led to the creation of a series of novel benzimidazole compounds with enhanced colistin adjuvant activity. Herein, we demonstrate that both IMD-0354 and a lead benzimidazole effectively restore colistin susceptibility in mouse models of highly colistin-resistant\n              <jats:italic>Klebsiella pneumoniae<\/jats:italic>\n              and\n              <jats:italic>Acinetobacter baumannii<\/jats:italic>\n              -induced peritonitis. These novel adjuvants show low toxicity\n              <jats:italic>in vivo<\/jats:italic>\n              , significantly reduce bacterial load, and prevent dissemination that could otherwise result in systemic infection.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/aac.00671-24","type":"journal-article","created":{"date-parts":[[2024,8,28]],"date-time":"2024-08-28T13:00:38Z","timestamp":1724850038000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":5,"title":["Adjuvants restore colistin sensitivity in mouse models of highly colistin-resistant isolates, limiting bacterial proliferation and dissemination"],"prefix":"10.1128","volume":"68","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1433-359X","authenticated-orcid":false,"given":"Beverly H.","family":"Koller","sequence":"first","affiliation":[{"name":"Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leigh A.","family":"Jania","sequence":"additional","affiliation":[{"name":"Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoting","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William T.","family":"Barker","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3548-3351","authenticated-orcid":false,"given":"Roberta J.","family":"Melander","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8271-4696","authenticated-orcid":false,"given":"Christian","family":"Melander","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1086\/533452"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12941-017-0191-3"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00006-08"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/160263a0"},{"key":"e_1_3_2_8_2","article-title":"Antibiotic activity of Bacillus polymyxa","volume":"54","author":"Benedict RG","year":"1947","unstructured":"Benedict RG, Langlykke AF. 1947. 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