{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T11:58:22Z","timestamp":1773316702599,"version":"3.50.1"},"reference-count":37,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2023,10,25]],"date-time":"2023-10-25T00:00:00Z","timestamp":1698192000000},"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":["RO1AI136904"],"award-info":[{"award-number":["RO1AI136904"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>In 2019, five million deaths associated with antimicrobial resistance were reported by The Centers for Disease Control and Prevention (CDC). Acinetobacter baumannii, a Gram-negative bacterial pathogen, is among the list of urgent threats. Previously, we reported 2-aminoimidazole (2-AI) adjuvants that potentiate macrolide activity against A. baumannii. In this study, we identify several of these adjuvants that sensitize A. baumannii to aminoglycoside antibiotics. Lead compounds 1 and 7 lower the tobramycin (TOB) minimum inhibitory concentration (MIC) against the TOB-resistant strain AB5075 from 128 \u03bcg\/mL to 2 \u03bcg\/mL at 30 \u03bcM. In addition, the lead compounds lower the TOB MIC against the TOB-susceptible strain AB19606 from 4 \u03bcg\/mL to 1 \u03bcg\/mL and 0.5 \u03bcg\/mL, respectively, at 30 \u03bcM and 15 \u03bcM. The evolution of resistance to TOB and 1 in AB5075 revealed mutations in genes related to protein synthesis, the survival of bacteria under environmental stressors, bacteriophages, and proteins containing Ig-like domains.<\/jats:p>","DOI":"10.3390\/antibiotics12111563","type":"journal-article","created":{"date-parts":[[2023,10,25]],"date-time":"2023-10-25T04:14:47Z","timestamp":1698207287000},"page":"1563","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Sensitization of Gram-Negative Bacteria to Aminoglycosides with 2-Aminoimidazole Adjuvants"],"prefix":"10.3390","volume":"12","author":[{"given":"Ashley N.","family":"Crotteau","sequence":"first","affiliation":[{"name":"Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Veronica B.","family":"Hubble","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Santiana A.","family":"Marrujo","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne E.","family":"Mattingly","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roberta J.","family":"Melander","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Melander","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,25]]},"reference":[{"key":"ref_1","unstructured":"CDC (2020). 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