Synergistic effect of MGB-BP3 and PAβN against resistant Escherichia coli

Abstract

Antibiotic resistance is considered to be a major top heath concern, especially Gram-negative bacteria, such as E. coli, which has several mechanisms to defeat antibiotics. Using combinations of antimicrobials might the best way to delay the deterioration in human heath because of resistant infections. The synergic effect of combining the novel antibacterial drug, MGB-BP3 that binds to the minor groove in DNA, with PAβN an efflux pump inhibitor, was determined through measuring minimum inhibitory concentrations (MICs).

A checkerboard assay was used to identify MICs and the subsequent fractional inhibitory concentration (FIC) Index. The checkerboard assay of four clinical strains of E. coli was performed on a 96-well plate using measured using OD600nm. The FIC for each drug can be obtained by dividing the MIC of the combined drug by the MIC of an individual drug, while the FIC index refers to the total of the FICs of each antibiotic evaluated.

To determine the synergistic effects, FICIs were calculated manually, and synergy scores were obtained by using SynergyFinder (https://synergyfinder.fimm.fi) ZIP model calculator. The MICs were decreased by between 10 and 80-fold for MGB-BP3 and between 5 and 21-folds for PAβN. Both manual calculations (≤0.5) and SynergyFinder data analysis (>10) agreed with each other.

The results suggest that combining MGB-BP3 with PABN shows promising synergistic activity against E. coli. However, this experiment has to be repeated and further studies on other efflux pump inhibitor (EPI) classes or minor groove DNA binder drugs are recommended.