The Possibilities of Reducing the Minimal Inhibitory Concentration of Puromycin and Ceftiofur in Their Combination with His6-OPH-Based Biologics

Abstract

Enzymes that hydrolyze the quorum-sensing signal molecules of pathogenic bacteria allow us to influence the number and stability of their populations. The combination of such enzymes with antibiotics can be considered as one of the ways of solving the problem of regulation of the development of antibiotic resistance. In the presence of puromycin and ceftiofur (0.2 g/L) during exposure at 25–41°C, the stabilization of His₆-OPH lactonase activity is observed. The molecular docking of antibiotics to the surface of the His₆- OPH dimer reveals the antibiotics binding both to the area near the active sites of the enzyme subunits and to the region of contact between the subunits of the dimer, which possibly led to the stabilization of the enzyme. The presence of enzyme preparations facilitates the reduction on 36–48% of the minimum inhibitory concentration (MIC) of puromycin and ceftiofur on the growth of highly concentrated (10⁶ cells/mL) cell populations of Pseudomonas aeruginosa B-6643 and Escherichia coli B-6645.