{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T15:19:34Z","timestamp":1777389574740,"version":"3.51.4"},"reference-count":47,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,2,3]],"date-time":"2022-02-03T00:00:00Z","timestamp":1643846400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:sec><jats:title>Objectives:<\/jats:title><jats:p>To evaluate the <jats:italic>in vitro<\/jats:italic> antibacterial, antibiofilm, and antivirulence activities of apramycin, comparatively to tobramycin, against a set of <jats:italic>P. aeruginosa<\/jats:italic> from chronically infected cystic fibrosis (CF) patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The activity of antibiotics against planktonic cells was assessed by performing MIC, MBC, and time-kill assays. The activity against mature biofilms was evaluated, in a microtiter plate, both in terms of dispersion (crystal violet assay) and residual viability (viable cell count). The effect of drug exposure on selected <jats:italic>P. aeruginosa<\/jats:italic> virulence genes expression was assessed by real-time Reverse Transcription quantitative PCR (RT-qPCR).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Apramycin MIC<jats:sub>90<\/jats:sub> and MBC<jats:sub>90<\/jats:sub> values were found at least fourfold lower than those for tobramycin. A comparable trend was observed for mucoid strains. Only 4 out of 24 strains (16.6%) showed an apramycin MIC higher than the epidemiological cut-off value of 64 mg\/L, whereas a higher resistance rate was observed for tobramycin (62.5%; <jats:italic>p<\/jats:italic> &amp;lt; 0.01 vs. apramycin). In time-kill analyses, both aminoglycosides were found bactericidal, although apramycin showed a more rapid effect and did not allow for regrowth. Apramycin generally stimulated biofilm biomass formation, whereas tobramycin showed opposite trends depending on the strain tested. Both drugs caused a highly significant, dose-dependent reduction of biofilm viability, regardless of strain and concentration tested. The exposure to apramycin and tobramycin caused increased expression of <jats:italic>mexA<\/jats:italic> and <jats:italic>mexC<\/jats:italic> (multidrug efflux pumps), whereas tobramycin specifically increased the expression of <jats:italic>aprA<\/jats:italic> (alkaline protease) and <jats:italic>toxA<\/jats:italic> (exotoxin A). Neither apramycin nor tobramycin showed cytotoxic potential toward IB3-1 bronchial epithelial CF cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our results warrant future pharmacokinetic and pharmacodynamic studies for supporting the rationale to repurpose apramycin, a veterinary aminoglycoside, for CF lung infections.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmicb.2021.801152","type":"journal-article","created":{"date-parts":[[2022,2,3]],"date-time":"2022-02-03T08:51:43Z","timestamp":1643878303000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["Repurposing the Veterinary Antibiotic Apramycin for Antibacterial and Antibiofilm Activity Against Pseudomonas aeruginosa From Cystic Fibrosis Patients"],"prefix":"10.3389","volume":"12","author":[{"given":"Giovanni","family":"Di Bonaventura","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Veronica","family":"Lupetti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabio","family":"Verginelli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"Giancristofaro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosemary","family":"Barbieri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giovanni","family":"Gherardi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arianna","family":"Pompilio","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,2,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0027943","article-title":"Phenotypes of non-attached Pseudomonas aeruginosa aggregates resemble surface attached biofilm.","volume":"6","author":"Alhede","year":"2011","journal-title":"PLoS One"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1315","DOI":"10.1016\/j.cmi.2020.12.004","article-title":"Efficacy of EBL-1003 (apramycin) against Acinetobacter baumannii lung infections in mice.","volume":"27","author":"Becker","year":"2020","journal-title":"Clin. 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