Возможная роль представителей кишечного микробиома в биотрансформации арил-, пиридилсодержащих фосфинов и их производных (по данным спектроскопии ЯМР 31Р)

Abstract

Organophosphorus compounds (OPCs) are used in many areas of human activity. Unique physicochemical properties and high biological activity not only determine the applied value of OPCs but also give them the properties of xenobiotics that are harmful to human health, which largely depend on the state of the endogenous microbiota. The purpose of this work is to assess the effect of pyridyl- and aryl-containing phosphines, their oxides, and sulfides on the growth of Bifidobacterium bifidum and Escherichia coli and to identify possible patterns of biotransformation of OPCs using 31P NMR spectroscopy. Bacteria were cultivated in thioglycollate medium containing the tested phosphorus compounds. At the stationary growth phase was determined the cell concentration and were recorded spectra 31P NMR. It was shown that the most reliable (p<0,05) and opposite effect on the growth dynamics of both species of bacteria was exhibited by phosphine sulfides 1 and 3: PS1 (pyridyl) reduced the population reproduction rate by 35–40%, and PS3 (aryl) increased it by 45–60%. At the same time, OPCs themselves were most likely not metabolized. Phosphine oxides reduced the average titer of bacteria compared to the control, and PO3 caused complete cell elimination after 24 hours cultivation. In the medium with PO2 was identified PS2 appeared, which may be caused by the biologically mediated process of oxide-to-sulfide conversion. All phosphines are chemically labile and they were oxidized abiotically to oxides and sulfides. Formed sulfides could be the reason for a significant increase (to 35%) in the growth rate bacteria population both species. Five new unidentified organophosphorus compounds (UPC) were recorded on medias with B. bifidum, some of which may belong to the products of biotransformation of the original OPCs. Some organic phosphates, homologous to the phosphine oxides tested, have a δp value neighboring to the taken NMR spectra. This may indicate the way of their biological transformation: oxidation of the CP bond in the phosphine oxides to an ester bond of organic phosphates. This ability of bifidobacteria to metabolize OPCs will make it possible to develop a therapeutic strategy based on the use of B. bifidum as a microorganism that degrades phosphorus-containing xenobiotics.