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O. V. Maslova, A. G. Aslanli, O. V. Senko, E. N. Efremenko
The possibilities of reducing the minimum inhibitory
concentration of puromycin and ceftiofur with their combination with His6-OPH-based
biologics
Abstract
Enzymes that hydrolyze quorum sensing
signal molecules of pathogenic bacteria allow to influence the number and
stability of their populations. The combination of such enzymes with
antibiotics can be considered as one of the ways to solve the problem of
regulating the development of antibiotic resistance. In the presence of
puromycin and ceftiofur (0.2 g/L) during exposure at 25–41 ºC
stabilization of His6-OPH lactonase activity was observed. Molecular
docking of antibiotics to the surface of His6-OPH dimer revealed the
antibiotics binding both to the area near active centers of the enzyme subunits
and to the region of contact between 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 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.
Key words: hexahistidine-containing
organophosphorus hydrolase, antibiotic, puromycin, ceftiofur, minimal
inhibitory concentrations.
Copyright (C) Chemistry Dept., Moscow State University, 2002
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