The crisis of antibiotic resistance necessitates the search of phytochemicals as potential antibacterial, anti-quorum sensing and antibiofilm forming agents. For the present study, fifteen (15) selected medicinal plants were evaluated to inhibit the biological activities of multi-drug resistant (MDR) pathogenic bacteria (Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis) associated with diabetic foot ulcer. Antibacterial activities revealed noteworthy minimum inhibitory concentration (MIC) values ≤1 mg/mL for thirteen (13) out of the sixty (60) plant extracts screened. The potent extracts included Euclea natalensis ethyl acetate (0.25 mg/mL), Aloe ferox methanol (0.5 mg/ml) and Warburgia salutaris aqueous (0.5 mg/mL) extracts. Chemical profiling of the active extracts using gas chromatography-mass spectrometry (GC-MS) identified neophytadiene, guanosine, squalene, cis megastigma-5,8-diene-4-one and sorbitol as prevalent compounds among the active extracts. Anti-quorum sensing activities of E. natalensis (ethyl acetate), A. ferox (methanol) and W. salutaris (aqueous) extracts ranged from 4.81 - 58.34% with E. natalensis (ethyl-acetate) showing the highest activity. Molecular docking against CviR protein showed selected compounds having high docking scores with sorbitol showing the highest score of -7.04 kcal/mol. Warburgia salutaris aqueous extract exhibited the highest biofilm inhibition (73%) against E. coli. Euclea natalensis, Aloe ferox and Warburgia salutaris compounds act as antagonist of N-acyl homoserine lactone (AHL) signaling, thus may serve as candidates in antipathogenic and antibiofilm phytomedicine development for MDR foot ulcer bacterial pathogens.The South African National Research Foundation (NRF) Thuthuka Grant and the South African Medical Research Council-Self Initiated Research (SAMRC-SIR).https://www.cell.com/heliyon/homeBiochemistryGeneticsMicrobiology and Plant PathologyPlant Production and Soil Scienc
