Screening of Inhibitory Activity of Narrow Fractions of Humic Substances towards Different Types of Class A β-Lactamases

IF 1 4区生物学 Q4 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Applied Biochemistry and Microbiology Pub Date : 2024-12-18 DOI:10.1134/S0003683824605791

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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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.

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腐殖质窄组分对不同类型A类β-内酰胺酶抑制活性的筛选

抑制参与细菌对β-内酰胺类抗生素产生耐药性的β-内酰胺酶有望恢复其作为抗菌药物的有效性。在本研究中，我们从不同来源的腐殖质中筛选了一些A类丝氨酸β-内酰胺酶的抑制活性，这些腐殖质代表了复杂的有机基质，以及它们通过酸度和极性分离得到的窄组分。用13C核磁共振谱对其结构和基团组成进行了表征；用傅里叶变换-离子回旋共振质谱法对窄馏分的分子组成进行了表征。褐煤ha -1腐植酸组分对多种ESBL （TEM-12、TEM-17、TEM-18）和抗抑制剂β-内酰胺酶TEM-34的抑制特异性最广：TEM-12、TEM-17、TEM-18和TEM-34的残留活性分别为52±5、52±5、40±4和58±6。获得的数据表明，最有效的窄组分的有效性与磺胺乙酮相当，磺胺乙酮是一种很有前途的新型抑制剂。这表明利用二维色谱对天然腐殖质物质进行精细分馏是可行的，这将为非β-内酰胺性质的β-内酰胺酶抑制剂开辟一个新的、广泛的来源。

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来源期刊

Applied Biochemistry and Microbiology 生物-生物工程与应用微生物

CiteScore

1.70

自引率

12.50%

发文量

审稿时长

6-12 weeks

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.