Author(s): Monteiro, Rosana Isabel Araújo ; Silva, Eduarda ; Pereira, Maria Olívia ; Sousa, Ana Margarida
Date: 2024
Persistent ID: https://hdl.handle.net/1822/94704
Origin: RepositóriUM - Universidade do Minho
Subject(s): airway mucus; antibiotic adjuvant; ciprofloxacin; cystic fibrosis; mucoid phenotype; organic acid; Pseudomonas aeruginosa; small colony variants; succinic acid; weak acid
Pseudomonas aeruginosa 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 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. © 2024 by the authors.
