Mechanistic Insights into Succinic Acid as an Adjuvant for Ciprofloxacin in Treating <i>Pseudomonas aeruginosa</i> Growing Within Cystic Fibrosis Airway Mucus
<i>Pseudomonas aeruginosa</i> is a major cause of chronic respiratory infections in patients with cystic fibrosis (CF), with biofilm formation contributing to its persistence and antibiotic resistance. This study aimed to gain insights into the mechanistic action of succinic acid as a ci...
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MDPI AG
2024-12-01
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| author | Rosana Monteiro Eduarda Silva Maria Olivia Pereira Ana Margarida Sousa |
| author_facet | Rosana Monteiro Eduarda Silva Maria Olivia Pereira Ana Margarida Sousa |
| author_sort | Rosana Monteiro |
| collection | DOAJ |
| description | <i>Pseudomonas aeruginosa</i> is a major cause of chronic respiratory infections in patients with cystic fibrosis (CF), with biofilm formation contributing to its persistence and antibiotic resistance. 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 <i>P. aeruginosa</i> 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. |
| format | Article |
| id | doaj-art-44154a6fcd034853acfc7310a5389fcf |
| institution | DOAJ |
| issn | 2076-2607 |
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| series | Microorganisms |
| spelling | doaj-art-44154a6fcd034853acfc7310a5389fcf2025-08-20T02:57:16ZengMDPI AGMicroorganisms2076-26072024-12-011212253810.3390/microorganisms12122538Mechanistic Insights into Succinic Acid as an Adjuvant for Ciprofloxacin in Treating <i>Pseudomonas aeruginosa</i> Growing Within Cystic Fibrosis Airway MucusRosana Monteiro0Eduarda Silva1Maria Olivia Pereira2Ana Margarida Sousa3Centre of Biological Engineering, LIBRO—Laboratório de Investigação em Biofilmes Rosário Oliveira, University of Minho, Campus de Gualtar, 4710-057 Braga, PortugalCentre of Biological Engineering, LIBRO—Laboratório de Investigação em Biofilmes Rosário Oliveira, University of Minho, Campus de Gualtar, 4710-057 Braga, PortugalCentre of Biological Engineering, LIBRO—Laboratório de Investigação em Biofilmes Rosário Oliveira, University of Minho, Campus de Gualtar, 4710-057 Braga, PortugalCentre of Biological Engineering, LIBRO—Laboratório de Investigação em Biofilmes Rosário Oliveira, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal<i>Pseudomonas aeruginosa</i> is a major cause of chronic respiratory infections in patients with cystic fibrosis (CF), with biofilm formation contributing to its persistence and antibiotic resistance. 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 <i>P. aeruginosa</i> 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.https://www.mdpi.com/2076-2607/12/12/2538succinic acidantibiotic adjuvant<i>Pseudomonas aeruginosa</i>ciprofloxacincystic fibrosissmall colony variants |
| spellingShingle | Rosana Monteiro Eduarda Silva Maria Olivia Pereira Ana Margarida Sousa Mechanistic Insights into Succinic Acid as an Adjuvant for Ciprofloxacin in Treating <i>Pseudomonas aeruginosa</i> Growing Within Cystic Fibrosis Airway Mucus Microorganisms succinic acid antibiotic adjuvant <i>Pseudomonas aeruginosa</i> ciprofloxacin cystic fibrosis small colony variants |
| title | Mechanistic Insights into Succinic Acid as an Adjuvant for Ciprofloxacin in Treating <i>Pseudomonas aeruginosa</i> Growing Within Cystic Fibrosis Airway Mucus |
| title_full | Mechanistic Insights into Succinic Acid as an Adjuvant for Ciprofloxacin in Treating <i>Pseudomonas aeruginosa</i> Growing Within Cystic Fibrosis Airway Mucus |
| title_fullStr | Mechanistic Insights into Succinic Acid as an Adjuvant for Ciprofloxacin in Treating <i>Pseudomonas aeruginosa</i> Growing Within Cystic Fibrosis Airway Mucus |
| title_full_unstemmed | Mechanistic Insights into Succinic Acid as an Adjuvant for Ciprofloxacin in Treating <i>Pseudomonas aeruginosa</i> Growing Within Cystic Fibrosis Airway Mucus |
| title_short | Mechanistic Insights into Succinic Acid as an Adjuvant for Ciprofloxacin in Treating <i>Pseudomonas aeruginosa</i> Growing Within Cystic Fibrosis Airway Mucus |
| title_sort | mechanistic insights into succinic acid as an adjuvant for ciprofloxacin in treating i pseudomonas aeruginosa i growing within cystic fibrosis airway mucus |
| topic | succinic acid antibiotic adjuvant <i>Pseudomonas aeruginosa</i> ciprofloxacin cystic fibrosis small colony variants |
| url | https://www.mdpi.com/2076-2607/12/12/2538 |
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