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This study aimed to gain insights into the mechanistic action of succinic acid as a ciprofloxacin adjuvant against clinically relevant CF isolates, including small colony variants and mucoid strains, and a ciprofloxacin-resistant strain grown within CF dense mucus. Time-kill assays in artificial CF mucus, along with planktonic and surface-attached biofilm experiments, were used to assess the activity of succinic acid alone and in combination with sublethal ciprofloxacin concentrations. Succinic acid demonstrated an adjuvant effect of ciprofloxacin against P. aeruginosa grown within CF mucus at pH levels below pKa1 during the early bacterial growth stages. In examining planktonic growth and biofilms under these conditions, we found that succinic acid demonstrated strong antibacterial and antibiofilm properties. Conversely, succinic acid activity decreased at later growth stages, though it enhanced the ciprofloxacin effect, especially against mucoid biofilms. Moreover, we noted that, in dense CF mucus, succinic acid activity was attenuated compared to a non-CF environment, indicating diffusion challenges. These findings underscore the potential of succinic acid as a therapeutic adjuvant for improving antibiotic treatment outcomes and overcoming biofilm-associated resistance in CF.<\/jats:p>","DOI":"10.3390\/microorganisms12122538","type":"journal-article","created":{"date-parts":[[2024,12,9]],"date-time":"2024-12-09T08:17:49Z","timestamp":1733732269000},"page":"2538","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Mechanistic Insights into Succinic Acid as an Adjuvant for Ciprofloxacin in Treating Pseudomonas aeruginosa Growing Within Cystic Fibrosis Airway Mucus"],"prefix":"10.3390","volume":"12","author":[{"given":"Rosana","family":"Monteiro","sequence":"first","affiliation":[{"name":"Centre of Biological Engineering, LIBRO\u2014Laborat\u00f3rio de Investiga\u00e7\u00e3o em Biofilmes Ros\u00e1rio Oliveira, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2661-9966","authenticated-orcid":false,"given":"Eduarda","family":"Silva","sequence":"additional","affiliation":[{"name":"Centre of Biological Engineering, LIBRO\u2014Laborat\u00f3rio de Investiga\u00e7\u00e3o em Biofilmes Ros\u00e1rio Oliveira, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal"}]},{"given":"Maria Olivia","family":"Pereira","sequence":"additional","affiliation":[{"name":"Centre of Biological Engineering, LIBRO\u2014Laborat\u00f3rio de Investiga\u00e7\u00e3o em Biofilmes Ros\u00e1rio Oliveira, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal"},{"name":"LABBELS\u2014Associate Laboratory, Braga\/Guimar\u00e3es, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8900-2656","authenticated-orcid":false,"given":"Ana Margarida","family":"Sousa","sequence":"additional","affiliation":[{"name":"Centre of Biological Engineering, LIBRO\u2014Laborat\u00f3rio de Investiga\u00e7\u00e3o em Biofilmes Ros\u00e1rio Oliveira, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal"},{"name":"LABBELS\u2014Associate Laboratory, Braga\/Guimar\u00e3es, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1542\/pir.2019-0212","article-title":"Cystic Fibrosis","volume":"42","author":"Dickinson","year":"2021","journal-title":"Pediatr. 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