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Updated: Aug 16, 2025
Antibiotic Efficacy Testing in an Ex vivo Model of Pseudomonas aeruginosa and Staphylococcus aureus Biofilms in the Cystic Fibrosis Lung
Published on: January 22, 2021
In Vitro Assessment on Designing Novel Antibiofilms of Pseudomonas aeruginosa Using a Computational Approach
Dian Rachmawati1, Mochammad Zakki Fahmi2, Muhammad Ikhlas Abdjan3
1Faculty of Medicine, Universitas Airlangga, Surabaya 60132, Indonesia.
Abstract:
An anti-biofilm that can inhibit the matrix of biofilm formation is necessary to prevent recurrent and chronic Pseudomonas aeruginosa infection. This study aimed to design compounds with a new mechanism through competitive inhibitory activity against phosphomannomutase/phosphoglucomutase (PMM/PGM), using in vitro assessment and a computational (in silico) approach. The active site of PMM/PGM was assessed through molecular redocking using L-tartaric acid as the native ligand and other small molecules, such as glucaric acid, D-sorbitol, and ascorbic acid. The docking program set the small molecules to the active site, showing a stable complex formation. Analysis of structural similarity, bioavailability, absorption, distribution, metabolism, excretion, and toxicity properties proved the potential application of ligands as an anti-biofilm. In vitro assessment with crystal violet showed that the ligands could reach up to 95.87% inhibition at different concentrations. The nitrocellulose membrane and scanning electron microscopic visualization showed that the untreated P. aeruginosa biofilm was denser than the ligand-treated biofilm.
Insights
New compounds targeting phosphomannomutase/phosphoglucomutase (PMM/PGM) effectively inhibit Pseudomonas aeruginosa biofilm formation. This research offers a promising strategy against chronic and recurrent infections by disrupting biofilm matrix development.
Area of Science:
- Microbiology
- Computational Chemistry
- Drug Discovery
Background:
- Recurrent and chronic *Pseudomonas aeruginosa* infections pose significant clinical challenges.
- Inhibition of biofilm matrix formation is crucial for preventing persistent infections.
- Novel therapeutic targets are needed to combat antibiotic-resistant bacterial strains.
Purpose of the Study:
- To design novel anti-biofilm compounds targeting phosphomannomutase/phosphoglucomutase (PMM/PGM).
- To investigate the inhibitory mechanism of small molecules against PMM/PGM using computational and in vitro methods.
- To evaluate the anti-biofilm efficacy of identified ligands against *Pseudomonas aeruginosa*.
Main Methods:
- In silico molecular docking and redocking simulations of PMM/PGM active site with potential ligands (glucaric acid, D-sorbitol, ascorbic acid).
- Assessment of ligand properties including structural similarity, bioavailability, ADMET (absorption, distribution, metabolism, excretion, toxicity).
- In vitro anti-biofilm assays using crystal violet staining, nitrocellulose membrane, and scanning electron microscopy (SEM).
Main Results:
- Molecular docking confirmed stable complex formation between PMM/PGM and tested ligands.
- Ligands demonstrated favorable pharmacokinetic and toxicity profiles, indicating potential therapeutic application.
- In vitro assays showed significant inhibition of *P. aeruginosa* biofilm formation, reaching up to 95.87% inhibition.
- SEM analysis revealed a less dense biofilm structure in ligand-treated samples compared to untreated controls.
Conclusions:
- The designed compounds exhibit potent anti-biofilm activity against *Pseudomonas aeruginosa* by inhibiting PMM/PGM.
- The study validates a novel therapeutic approach targeting biofilm matrix synthesis.
- These findings provide a foundation for developing new treatments for biofilm-related infections.
