{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T02:12:53Z","timestamp":1782439973492,"version":"3.54.5"},"reference-count":68,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,2,3]],"date-time":"2023-02-03T00:00:00Z","timestamp":1675382400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Health","doi-asserted-by":"publisher","award":["2R15AI047115"],"award-info":[{"award-number":["2R15AI047115"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Health","doi-asserted-by":"publisher","award":["SC3GM125556"],"award-info":[{"award-number":["SC3GM125556"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Health","doi-asserted-by":"publisher","award":["T37MD001368"],"award-info":[{"award-number":["T37MD001368"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Institute on Minority Health and Health Disparities","award":["2R15AI047115"],"award-info":[{"award-number":["2R15AI047115"]}]},{"name":"National Institute on Minority Health and Health Disparities","award":["SC3GM125556"],"award-info":[{"award-number":["SC3GM125556"]}]},{"name":"National Institute on Minority Health and Health Disparities","award":["T37MD001368"],"award-info":[{"award-number":["T37MD001368"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Plazomicin is a recent U.S. Food and Drug Administration (FDA)-approved semisynthetic aminoglycoside. Its structure consists of a sisomicin scaffold modified by adding a 2(S)-hydroxy aminobutyryl group at the N1 position and a hydroxyethyl substituent at the 6\u2032 position. These substitutions produced a molecule refractory to most aminoglycoside-modifying enzymes. The main enzyme within this group that recognizes plazomicin as substrate is the aminoglycoside 2\u2032-N-acetyltransferase type Ia [AAC(2\u2032)-Ia], which reduces the antibiotic\u2019s potency. Designing formulations that combine an antimicrobial with an inhibitor of resistance is a recognized strategy to extend the useful life of existing antibiotics. We have recently found that several metal ions inhibit the enzymatic inactivation of numerous aminoglycosides mediated by the aminoglycoside 6\u2032-N-acetyltransferase type Ib [AAC(6\u2032)-Ib]. In particular, Ag+, which also enhances the effect of aminoglycosides by other mechanisms, is very effective in interfering with AAC(6\u2032)-Ib-mediated resistance to amikacin. Here we report that silver acetate is a potent inhibitor of AAC(2\u2032)-Ia-mediated acetylation of plazomicin in vitro, and it reduces resistance levels of Escherichia coli carrying aac(2\u2032)-Ia. The resistance reversion assays produced equivalent results when the structural gene was expressed under the control of the natural or the blaTEM-1 promoters. The antibiotic effect of plazomicin in combination with silver was bactericidal, and the mix did not show significant toxicity to human embryonic kidney 293 (HEK293) cells.<\/jats:p>","DOI":"10.3390\/ph16020236","type":"journal-article","created":{"date-parts":[[2023,2,6]],"date-time":"2023-02-06T02:29:23Z","timestamp":1675650563000},"page":"236","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Inhibition of Enzymatic Acetylation-Mediated Resistance to Plazomicin by Silver Ions"],"prefix":"10.3390","volume":"16","author":[{"given":"David","family":"Ngo","sequence":"first","affiliation":[{"name":"Center for Applied Biotechnology Studies, Department of Biological Science, California State University Fullerton, Fullerton, CA 92831, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angel J.","family":"Maga\u00f1a","sequence":"additional","affiliation":[{"name":"Center for Applied Biotechnology Studies, Department of Biological Science, California State University Fullerton, Fullerton, CA 92831, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tung","family":"Tran","sequence":"additional","affiliation":[{"name":"Center for Applied Biotechnology Studies, Department of Biological Science, California State University Fullerton, Fullerton, CA 92831, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Sklenicka","sequence":"additional","affiliation":[{"name":"Center for Applied Biotechnology Studies, Department of Biological Science, California State University Fullerton, Fullerton, CA 92831, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberly","family":"Phan","sequence":"additional","affiliation":[{"name":"Center for Applied Biotechnology Studies, Department of Biological Science, California State University Fullerton, Fullerton, CA 92831, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Eykholt","sequence":"additional","affiliation":[{"name":"Center for Applied Biotechnology Studies, Department of Biological Science, California State University Fullerton, Fullerton, CA 92831, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0744-8137","authenticated-orcid":false,"given":"Ver\u00f3nica","family":"Jimenez","sequence":"additional","affiliation":[{"name":"Center for Applied Biotechnology Studies, Department of Biological Science, California State University Fullerton, Fullerton, CA 92831, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9904-7890","authenticated-orcid":false,"given":"Mar\u00eda S.","family":"Ramirez","sequence":"additional","affiliation":[{"name":"Center for Applied Biotechnology Studies, Department of Biological Science, California State University Fullerton, Fullerton, CA 92831, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6298-7811","authenticated-orcid":false,"given":"Marcelo E.","family":"Tolmasky","sequence":"additional","affiliation":[{"name":"Center for Applied Biotechnology Studies, Department of Biological Science, California State University Fullerton, Fullerton, CA 92831, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,3]]},"reference":[{"key":"ref_1","first-page":"65","article-title":"Bad bugs, no drugs 2002\u20132020: Progress, challenges, and call to action","volume":"131","author":"Boucher","year":"2020","journal-title":"Trans. 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