Capsaicin inhibits the biofilm of Klebsiella pneumoniae by targeting the transcriptional regulator SdiA

• Published in: Microbial pathogenesis Vol. 207; p. 107860
• Main Authors: Xue, Yang, Yan, An
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.10.2025
• Subjects: Anti-Bacterial Agents - pharmacology; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Biofilm; Biofilms - drug effects; Biofilms - growth & development; Capsaicin; Capsaicin - pharmacology; Gene Expression Regulation, Bacterial - drug effects; Humans; Hydrophobic and Hydrophilic Interactions - drug effects; Klebsiella pneumoniae; Klebsiella pneumoniae - drug effects; Klebsiella pneumoniae - genetics; Klebsiella pneumoniae - growth & development; Microbial Sensitivity Tests; Microscopy; Molecular docking; Molecular Docking Simulation; Polysaccharides, Bacterial - metabolism; Reactive Oxygen Species - metabolism; SdiA; Trans-Activators - genetics; Trans-Activators - metabolism; Biofilm; Microscopy; Capsaicin; Klebsiella pneumoniae; SdiA; Molecular docking
• ISSN: 0882-4010; 1096-1208; 1096-1208
• DOI: 10.1016/j.micpath.2025.107860

Pneumonia, particularly when caused by the bacterium Klebsiella pneumoniae, presents a major global health challenge. This gram-negative bacterium is a notable pathogen in healthcare-associated infections, leading to severe conditions such as urinary tract infections, pneumonia, and the bloodstream infections, mainly in immunocompromised subjects. The bacterium's ability to resist multiple antibiotics complicates the treatment, posing a major concern in hospital settings. Capsaicin, one the major capsaiciniods present in Capsicum plants, is known for the bacteriostatic and bactericidal properties, though detailed studies on effects of capsaicin on biofilm in K. pneumoniae is not thoroughly investigated. Preliminary analyses indicate that capsaicin can inhibit the growth of K. pneumoniae at MIC (256 μg/ml). Capsaicin effectively inhibits biofilm development (72.65 ± 3.23 %) and reduces the metabolic activity (46.64 ± 4.31 %) of biofilms. Furthermore, exopolysaccharide production was diminished along with the eradication of established biofilm by capsaicin. Treatment of capsaicin decreased the cell surface hydrophobicity and induced the intracellular ROS production. The transcription level of biofilm and QS-related genes were also downregulated in presence of capsaicin. Computational analysis revealed that capsaicin interacts with transcriptional regulator SdiA with binding energy −5.6 kcal/mol. Molecular simulations validated the stability of SdiA-capsaicin complex under physiological conditions. The complex was mainly stabilized by the van der Waals forces. This study shows the potential of capsaicin in managing pneumonia complications, particularly those caused by K. pneumoniae. The findings suggest that capsaicin may serve as a promising agent in development of new therapeutic drug to combat bacterial infections associated with biofilm and antibiotic resistance. •Capsaicin inhibits K. pneumoniae reduces biofilm formation at sub-MIC.•Capsaicin reduced metabolic activity and exopolysaccharide production.•Capsaicin downregulates QS and biofilm-related gene expression in K. pneumoniae.•Capsaicin binds SdiA with −5.6 kcal/mol binding energy and forms stable complex.