Abstract Description

Campylobacter jejuni is a leading cause of foodborne bacterial gastroenteritis, with increasing antibiotic resistance underscoring a significant public health challenge. Efflux pumps and membrane permeability are imperative in multidrug resistance (MDR), necessitating alternative therapeutic strategies. This study explored the potential of natural products, specifically seasonal propolis extracts, to mitigate MDR in C. jejuni targeting efflux pumps and the outer membrane permeability using in vitro and in silico approaches. South African propolis extracts were screened against C. jejuni, using the broth microdilution method, efflux pump and membrane disruption assays. Winter extract showed a noteworthy minimum inhibitory concentration of 90 µg/ml. For the identification of tentative compounds present in the extracts, GC-MS analysis was used and revealed major phenolic and flavonoid compounds such as galangin, pinocembrin, totarol, and ferruginol. Molecular docking of these compounds against efflux pump protein (CmeABC: 5lq3) and outer membrane porin (MOMP: 5ldv), showed high binding affinities (-7.0kcal/mol to -8.2kcal/mol). Further validation through molecular dynamics simulations (MDS) under the following parameters: root mean square deviation (RMSD), root mean square fluctuation (RMSF), radius of gyration (Rog), and solvent accessible surface area (SASA) demonstrate propolis potential to effectively inhibit efflux pump activity and increase membrane permeability. These findings highlight propolis as a promising natural alternative to combat C. jejuni resistance by targeting efflux mechanisms and membrane integrity.