P-1533. In silico Exploration of Cannabidiol Interactions with Outer Membrane Proteins in Salmonella Typhimurium LT2

TL;DR

This study uses computer modeling to explore how cannabidiol interacts with proteins in Salmonella bacteria, suggesting it could be a new antimicrobial treatment.

Contribution

The study identifies specific outer membrane proteins in Salmonella that CBD binds to, with insights into binding affinities and interactions.

Findings

CBD showed highest binding affinity with OmpX and NompC proteins at -6.6 and -6.4 kcal/mol.

CBD interacts with OMPs through hydrogen bonds, π-stacking, and hydrophobic interactions.

Phylogenetic analysis revealed high sequence conservation among OMPs across S. Typhimurium strains.

Abstract

Cannabidiol (CBD), the non-psychoactive component of the hemp plant has an enormous potential as a novel antimicrobial agent. Several studies have explored CBD’s potential as a potent alternative antimicrobial agent against both Gram-Negative and Gram-Positive pathogens. However, the exact mechanisms or specific interactions between CBD and the membrane is poorly understood.

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. OmpX and NompC exhibited the highest binding affinity with CBD at -6.6 kcal/mol and -6.4 kcal/mol respectively. The results also revealed several key interactions such as conventional hydrogen bonds, π-stacking, and hydrophobic interactions which plays crucial roles in the stability of the binding complex. We also included phylogenetic analysis of fifty different strains of S. Typhimurium, and observed high sequence conservation levels among the OMPs, at a sequence similarity threshold of 90%. This high conservation underscores the importance of targeting the conserved regions for the efficient use of CBD as a broad-spectrum antibiotic.

This may enhance the efficacy of existing antimicrobial treatments. In conclusion, the in silico findings suggest that CBD, through its interaction with critical OMPs, has the potential to serve as a potent antimicrobial agent against S. Typhimurium LT2. Especially when CBD is formulated to target the conserved regions of the OMPs. These findings are preliminary with several limitations. In vitro and in vivo studies may be required to validate the findings in this study, laying the foundation for further studies on CBD as a novel therapeutic agent in combating bacterial infections and addressing the global challenge of antibiotic resistance.

All Authors: No reported disclosures