{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:45:04Z","timestamp":1790210704727,"version":"4.1.0"},"reference-count":30,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,4,12]],"date-time":"2021-04-12T00:00:00Z","timestamp":1618185600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004191","name":"Novo Nordisk","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004191","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005111","name":"Rigshospitalet","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005111","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p><jats:italic>Pseudomonas aeruginosa<\/jats:italic> is known to contribute to the pathogenesis of chronic wounds by biofilm-establishment with increased tolerance to host response and antibiotics. The neutrophil-factor S100A8\/A9 has a promising adjuvant effect when combined with ciprofloxacin, measured by quantitative bacteriology, and increased anti- and lowered pro-inflammatory proteins. We speculated whether a S100A8\/A9 supplement could prevent ciprofloxacin resistance in infected wounds.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>Full-thickness 2.9cm<jats:sup>2<\/jats:sup>-necrosis was inflicted on 32 mice. On day 4, <jats:italic>P.aeruginosa<\/jats:italic> in seaweed alginate was injected sub-eschar to mimic a mono-pathogenic biofilm. Mice were randomized to receive ciprofloxacin and S100A8\/A9 (n=14), ciprofloxacin (n=12) or saline (n=6). Half of the mice in each group were euthanized day 6 and the remaining day 10 post-infection. Mice were treated until sacrifice. Primary endpoint was the appearance of ciprofloxacin resistant <jats:italic>P.aeruginosa<\/jats:italic>. The study was further evaluated by genetic characterization of resistance, means of quantitative bacteriology, wound-size and cytokine-production.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Three mice receiving ciprofloxacin monotherapy developed resistance after 14 days. None of the mice receiving combination therapy changed resistance pattern. Sequencing of fluoroquinolone-resistance determining regions in the ciprofloxacin resistant isolates identified two high-resistant strains mutated in <jats:italic>gyrA<\/jats:italic> C248T (MIC&amp;gt;32\u00b5g\/ml) and a <jats:italic>gyr B<\/jats:italic> mutation was found in the sample with low level resistance (MIC=3\u00b5g\/ml). Bacterial densities in wounds were lower in the dual treated group compared to the placebo group on both termination days.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study supports the ciprofloxacin augmenting effect and indicates a protective effect in terms of hindered ciprofloxacin resistance of adjuvant S100A8\/A9 in <jats:italic>P.aeruginosa<\/jats:italic> biofilm infected chronic wounds.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcimb.2021.652012","type":"journal-article","created":{"date-parts":[[2021,4,12]],"date-time":"2021-04-12T07:38:47Z","timestamp":1618213127000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Adjunctive S100A8\/A9 Immunomodulation Hinders Ciprofloxacin Resistance in Pseudomonas aeruginosa in a Murine Biofilm Wound Model"],"prefix":"10.3389","volume":"11","author":[{"given":"Anne S.","family":"Laulund","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franziska","family":"Schwartz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah","family":"Tr\u00f8strup","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim","family":"Thomsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Christophersen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik","family":"Calum","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oana","family":"Ciofu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niels","family":"H\u00f8iby","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claus","family":"Moser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,4,12]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00320-18","article-title":"Evolution of Antibiotic Resistance in Biofilm and Planktonic Pseudomonas aeruginosa Populations Exposed to Subinhibitory Levels of Ciprofloxacin","volume":"62","author":"Ahmed","year":"2018","journal-title":"Antimicrob. 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