V. G. Grigorenko, M. Yu. Rubtsova, I. P. Andreeva, G. V. Presnova, T. A. Mikhnevich, S. Yiming, D. S. Kravtsova, A. I. Konstantinov, D. A. Arutyunyan, I. V. Perminova
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引用次数: 0
Abstract
Inhibition of β-lactamases involved in the development of bacterial resistance to β-lactam antibiotics is promising for restoring their effectiveness as antibacterial drugs. In this work, we screened the inhibitory activity against some serine β-lactamases of class A among humic substances of various origins, which represent complex organic matrices, as well as their narrow fractions obtained by separating preparations by acidity and polarity. The structural and group composition of broad fractions was characterized by 13C NMR spectroscopy; the molecular composition of narrow fractions was characterized by Fourier transform-ion cyclotron resonance mass spectrometry. The widest specificity of inhibition against various ESBL (TEM-12, TEM-17, TEM-18) and the inhibitor-resistant β-lactamase TEM-34 was possessed by the fraction of humic acids of brown coal CHA-I, isolated at pH 9: the values of residual activity of TEM -12, TEM-17, TEM-18, and TEM-34 were (%) 52 ± 5, 52 ± 5, 40 ± 4, and 58 ± 6, respectively. The data obtained for the most active narrow fraction turned out to be comparable to the effectiveness of sulfohydantoins, a promising new class of inhibitors. This indicates the feasibility of further work on the fine fractionation of natural humic substances using 2D chromatography, which will open a new, extensive source of β-lactamase inhibitors of non-β-lactam nature.
期刊介绍:
Applied Biochemistry and Microbiology is an international peer reviewed journal that publishes original articles on biochemistry and microbiology that have or may have practical applications. The studies include: enzymes and mechanisms of enzymatic reactions, biosynthesis of low and high molecular physiologically active compounds; the studies of their structure and properties; biogenesis and pathways of their regulation; metabolism of producers of biologically active compounds, biocatalysis in organic synthesis, applied genetics of microorganisms, applied enzymology; protein and metabolic engineering, biochemical bases of phytoimmunity, applied aspects of biochemical and immunochemical analysis; biodegradation of xenobiotics; biosensors; biomedical research (without clinical studies). Along with experimental works, the journal publishes descriptions of novel research techniques and reviews on selected topics.