Cannabidiol Interactions with Outer Membrane Proteins in Salmonella Typhimurium LT2

Cannabidiol (CBD), the non-psychoactive component of the hemp plant has tremendous potential as a novel antimicrobial agent. This study aimed at understanding the interactions between CBD and the outer membrane proteins (OMPs) of Salmonella Typhimurium LT2. Employing in silico techniques, we analyzed the binding affinities, interaction dynamics, and drug-likeness of CBD with key OMPs such as OmpA, OmpC, OmpD, OmpF, OmpX, and NompC. The molecular docking results showed that CBD exhibits varying binding affinities across the OMPs, with OmpX and NompC showing the highest binding affinity of -6.6 kcal/mol and − 6.4 kcal/mol respectively, indicating strong and stable interactions. The results also revealed several key interactions such as hydrogen bonds, Pi-stacking, and hydrophobic interactions, playing crucial roles in the stability and specificity of these protein-ligand complexes. Notable interactions were identified in OmpA with a binding affinity of -5.9 kcal/mol involving hydrogen bonds at 3.2 Å and Pi-Sigma interactions at 3.4 Å. We included phylogenetic analysis of fifty different strains of Salmonella Typhimurium, and we observed high conservation levels among the OMPs, with a sequence similarity threshold of 90%. This high conservation underscores the potential of CBD to act as a broad-spectrum antimicrobial agent. Furthermore, our comparative structural analysis revealed both conserved and variable regions within the OMPs, highlighting the significance of targeting these regions to mitigate resistance development. Using KEGG Pathway analysis, we analyzed OmpC and OmpF, given their roles in nutrient transport and permeability. The disruption of these pathways by CBD binding could impair the bacteria’s ability to manage environmental stresses and evade host immune responses. Beta-lactam resistance pathway analysis was also considered, we observed that CBD could potentially disrupt resistance mechanisms by binding to OMPs, enhancing the efficacy of existing antimicrobial treatments. In conclusion, our findings suggest that CBD, through its interaction with critical OMPs, has the potential to serve as a potent antimicrobial agent against Salmonella Typhimurium LT2. These findings lay the foundation for further studies of CBD as a novel therapeutic agent in combating bacterial infections and addressing the global challenge of antibiotic resistance.