In vitro antibiofilm activity-directed in silico identification of natural products targeting bacterial biofilm regulators SarA and LasR

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Shilpi, Jamil A. and Sarker, Dipto Kumer and Seidel, Veronique and Ali, Mohammad Tuhin and Uddin, Shaikh Jamal and Basak, Ananya and Chakraborty, Shaown and Khairuzzaman, M and Nahar, Akhlak Un and Salam, Fayad Bin Abdus (2025) In vitro antibiofilm activity-directed in silico identification of natural products targeting bacterial biofilm regulators SarA and LasR. Current Pharmaceutical Biotechnology. ISSN 1873-4316 (https://doi.org/10.2174/01138920103488552411130313...)

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Abstract

Background: Antibiofilm agents serve as an essential tool in the fight against antibiotic resistance, and natural products provide a promising source for potential drug leads. Objective: This study investigates the activity of twenty Bangladeshi medicinal plants against Staphylococcus aureus and Pseudomonas aeruginosa biofilms and predicts the interactions of selected phytochemicals from five of the best performing plants with the active sites of transcriptional regulatory proteins SarA of S. aureus and LasR of P. aeruginosa. Methods: The plant extracts were tested by microtiter plate-based assay against S. aureus and P. aeruginosa biofilms. Molecular docking and molecular dynamics simulation (MD) were conducted using PyRx and GROMACS, respectively. Results: The best activity was identified for Cassia fistula and Ananas comosus, showing ≥ 75% inhibition of biofilm formation. ent-Epicatechin-(4α→8)-epiafzelechin (EEE) of C. fistula, cyanidin-3,3',5-tri-O-β-D-glucopyranoside (CTG) of A. comosus, and 7-O-(4-hydroxy-Ecinnamoyl)- spinoside of A. spinosus showed the best predictive binding affinity (-7.6, -7.6 and - 7.7 kcal/mol, respectively) for SarA. EEE was the only ligand to exhibit a stable ligand-protein complex with SarA in the MD simulation of 200 ns (binding energy of MMPBSA analysis - 39.899 kJ/mol). Chrysophanol, epicatechin and physcion, of C. fistula (-10.5, -10.5, and -11.0 kcal/mol, respectively) and auraptene of F. limonia (-10.8 kcal/mol) showed the best predictive binding affinity for LasR. Epicatechin showed the most stable ligand-protein complex with LasR (binding energy of MMPBSA analysis -63.717 kJ/mol) Conclusion: Epicatechin and its derivative EEE could be used as scaffolds for the development of new antibiofilm agents against P. aeruginosa and S. aureus, respectively.

ORCID iDs

Shilpi, Jamil A., Sarker, Dipto Kumer, Seidel, Veronique ORCID logoORCID: https://orcid.org/0000-0003-3880-5261, Ali, Mohammad Tuhin, Uddin, Shaikh Jamal, Basak, Ananya, Chakraborty, Shaown, Khairuzzaman, M, Nahar, Akhlak Un and Salam, Fayad Bin Abdus;
CORE (COnnecting REpositories)