Medicine in Drug Discovery (Dec 2023)
Bac-EPIC: A web interface for developing novel efflux pump inhibitor compounds targeting Escherichia coli
Abstract
Multidrug resistance (MDR) poses a severe threat to human health. The existence of efflux pumps primarily contributes to resistance in Gram-negative bacterial infections. Efflux pump inhibitors (EPIs) can potentially improve the efficacy of antibiotics and reduce bacterial pathogenicity by inhibiting the mechanism of these pumps. Here we report Bac-EPIC, a web interface consisting of AcrA_Ipred, and AcrB_Ipred tools, can aid in the identification of potential EPIs that might bind to AcrAB-TolC pump subunits, alter its structure in vivo, prevent efflux, and enhance antibiotic efficacy in Escherichia coli (E. coli) and other Gram-negative bacteria. The web server is developed by collecting and archiving structural moieties from literature-reported EPIs. The web interface can be utilized in decision-making upon structural similarity-based screening on whether a compound should be examined experimentally or disregarded. It takes the SMILES format of chemical structure as an input. Users can also draw the 2D structure and get the output report of the possible structural similarity profile, similarity percentage, and the active moieties in the compound. The designed web interface is publicly accessible for in silico efflux pump inhibition prediction, at http://14.139.62.46/AcrAB_Ipred/. Overall, the webserver increases the diversity of EPIs, and proposes mechanistic insights to understand and regulate the efflux pump assembly & its function, ultimately aiding in fight against antibiotic resistance.
