Influence of oxo-derivatives of nitrogen containing heterocycles CBR-384 and CBR-386 on respiratory activity and the level of extracellular sulfur containing compounds in Escherichia coli
DOI:
https://doi.org/10.17072/1994-9952-2023-4-367-374Keywords:
Escherichia coli, respiration, membrane potential, glutathione, H2SAbstract
The biological activity of two representatives of oxo-derivative nitrogen-containing heterocycles CBR-384 and CBR-386, planned for use as drugs, on growing aerobically gram-negative bacteria Escherichia coli was studied. Compound CBR-384 completely inhibited growth rate and biomass accumulation as measured by optical density (OD600). Continuous recording of dissolved oxygen (dO2) with a Clark electrode directly in the growing culture showed that CBR-384 caused a rapid and irreversible increase in oxygen levels in the medium, which indicated a decrease in the respiratory activity of cells. In time, the phase of rapid decline in respiration coincided with the phase of decreased growth rate. In aerobic cultures of E. coli, respiratory activity is closely related to the generation of membrane potential. However, only a small, but statistically significant, decrease in membrane potential, measured using the fluorescent dye DiBAC4(3), was found with CBR-384. It is known that in aerobic E. coli cultures growing on sulfate as a sulfur source, stress-induced growth inhibition is accompanied by an increase in extracellular glutathione (GSH) and H2S export. The use of a sulfide-specific electrode revealed that when E. coli growth is stopped by CBR-384, sulfide is also exported into the medium. Under these conditions, an increase in extracellular GSH was also noted. The effect of CBR-386 on E. coli, assessed by these four parameters, was less pronounced. The differences in the biological activities of CBR-384 and CBR-386 may be due to differences in their structures.References
Boteva A.A. et al. Synthesis and analgesic activity of [b]-annelated 4-quinolones // Pharmaceutical Chemistry Journal. 2019. Vol. 53. P. 616–619. DOI: 10.1007/s11094-019-02048-2
Enright E.F. et al. The impact of the gut microbiota on drug metabolism and clinical outcome // Yale Journal of Biology and Medicine. 2016. Vol. 89. P. 375–382.
Gao J., Hou H., Gao F. Current scenario of quinolone hybrids with potential antibacterial activity against ESKAPE pathogens // European Journal of Medicinal Chemistry. 2023. Vol. 247. № 115026. DOI: 10.1016/j.ejmech.2022.115026
Jiang S. et al. Anti-cancer activity of benzoxazinone derivatives via targeting c-Myc G-quadruplex struc-ture // Life Sciences. 2020. V. 258. № 118252. DOI: 10.1016/j.lfs.2020.118252
Kho Z.Y., Lal S.K. The human gut microbiome - a potential controller of wellness and disease // Frontiers in Microbiology. 2018. Vol. 9. № 1835. DOI: 10.3389/fmicb.2018.01835
Marchesi J.R., Ravel J. The vocabulary of microbiome research: a proposal // Microbiome. 2015. Vol. 3. № 31. DOI: 10.1186/s40168-015-0094-5
Miller J.H. Experiments in molecular genetics // New York: Cold Spring Harbor Laboratory Press. 1972. 466 p.
Rowland I. et al. Gut microbiota functions: metabolism of nutrients and other food components // Euro-pean Journal of Nutrition. 2018. Vol. 57. P. 1–24. DOI: 10.1007/s00394-017-1445-8
Smirnova G.V., Oktyabrsky O.N. Glutathione in bacteria // Biochemistry (Moscow). 2005. Vol. 70. P. 1199–1211. DOI: 10.1007/s10541-005-0248-3
Smirnova G., Muzyka N., Oktyabrsky O. Transmembrane glutathione cycling in growing Escherichia coli cells // Microbiological Research. 2012. Vol. 167. P. 166-172. DOI: 10.1016/j.micres.2011.05.005
Smirnova G.V. et al. Extracellular superoxide provokes glutathione efflux from Escherichia coli cells // Research in Microbiology. 2015. V. 166. P. 609–617. DOI: 10.1016/j.resmic.2015.07.007
Tietze F. Enzymic method for quantitative determination of nanogram amounts of total and oxidized glutathione: applications to mammalian blood and other tissues // Analytical Biochemistry. 1969. Vol. 27. P. 502-522. DOI: 10.1016/0003-2697(69)90064-5
Tyulenev A.V. et al. The role of sulfides in stress-induced changes of Eh in Escherichia coli cultures // Bioelectrochemistry. 2018. Vol. 121. P. 11–17. DOI: 10.1016/j.bioelechem.2017.12.012
White A.P. et al. Intergenic sequence comparison of Escherichia coli isolates reveals lifestyle adapta-tions but not host specificity // Applied Environmental Microbiology. 2011. Vol. 77. P. 7620–7632. DOI: 10.1128/AEM.05909-11
Wickens H.J. et al. Flow cytometric investigation of filamentation, membrane patency and membrane potential in Escherichia coli following ciprofloxacin exposure // Antimicrobial Agents and Chemotherapy. 2000. Vol. 44. P. 682–687. DOI: 10.1128/AAC.44.3.682-687.2000
Wilson I.D., Nicholson J.K. Gut microbiome interactions with drug metabolism, efficacy, and toxicity // Translational Research. 2017. V. 179. P. 204–222. DOI: 10.1016/j.trsl.2016.08.002