Molecular insights in potentiation of antibiotic activity by apple cider vinegar in diabetic wound pathogens

Abstract Background The prevalence of antibiotic resistance has become a critical global health concern. In particular, resistant strains of S taphylococcus aureus (SA) and Pseudomonas aeruginosa (PA) against commonly prescribed antibiotics for various infections are on the rise . These pathogens are frequently implicated in severe and complex infections, e.g., diabetic foot infections (DFI), posing a significant antimicrobial challenges during treatment. Frequently used food grade product, i.e., apple cider vinegar (ACV) carries promising antimicrobial potential. Therefore, the study designed to investigate the potential of ACV in combination with antibiotics to determine the effectiveness of the combination in overall pathogenic burden. Results Antimicrobial sensitivity was evaluated using disk diffusion and broth dilution techniques, revealing that at 2.5% acidity, ACV has prominent inhibitory potential against SA and PA . The fractional inhibitory concentration (FIC) index further confirmed synergistic interplay of ACV in combination with antibiotics. The results for minimum bactericidal concentration (MBC) showed when ACV is added to existing antibiotics the MBC value after checkerboard analysis method comes out to be, 128 µg/mL, 128 µg/mL, 64 µg/mL, and 64 µg/mL for amoxicillin, cefotaxime, imipenem, and vancomycin, respectively, against SA whereas concentration of 128 µg/mL, 256 µg/mL, 256 µg/mL, and 128 µg/mL MBC values for respective antibiotics against PA . Quantitative PCR analysis has demonstrated a substantial reduction in the expression of resistance-conferring genes when ACV was combined with antibiotics. Furthermore, molecular docking analysis showed ACV’s active constituents, such as acetic acid and chlorogenic acid, exhibited strong binding affinities against resistant conferring genes and subsequent proteins expression. These findings suggest that ACV may alter permeability of the outer membrane porin channels, thereby improving antibiotic penetration and augmented antimicrobial efficacy. Conclusion The study demonstrated that ACV not only improves antibiotic permeability within bacterial cell but also significantly augments bactericidal activity of these agents against resistant strains of SA and PA . The combination of various concentrations of ACV with antibiotics presents an innovative therapeutic strategy to combat current antimicrobial resistance, particularly in the treatment and management of complex DFI. These findings underscore the potential of integrating food grade products with conventional antibiotics to address the growing challenges of antibiotic resistance.