Interaction of 5-substituted pyrimidine nucleoside analogues and M.Tuberculosis: A view through an electron microscope

Anastasia L Khandazhinskaya; Elena S Matyugina; Liudmila A Alexandrova; Vasiliy A Kezin; Larisa N Chernousova; Tatiana G Smirnova; Sofya N Andreevskaya; Vladimir I Popenko; Olga G Leonova; Sergey N Kochetkov

doi:10.1016/j.biochi.2020.03.004

Interaction of 5-substituted pyrimidine nucleoside analogues and M.Tuberculosis: A view through an electron microscope

Biochimie. 2020 Apr-May:171-172:170-177. doi: 10.1016/j.biochi.2020.03.004. Epub 2020 Mar 6.

Affiliations

¹ Engelhardt Institute of Molecular Biology of the Russian Academy of Sciences, 32 Vavilov St., Moscow, 119991, Russia. Electronic address: [email protected].
² Engelhardt Institute of Molecular Biology of the Russian Academy of Sciences, 32 Vavilov St., Moscow, 119991, Russia. Electronic address: [email protected].
³ Engelhardt Institute of Molecular Biology of the Russian Academy of Sciences, 32 Vavilov St., Moscow, 119991, Russia. Electronic address: [email protected].
⁴ Engelhardt Institute of Molecular Biology of the Russian Academy of Sciences, 32 Vavilov St., Moscow, 119991, Russia.
⁵ Central Tuberculosis Research Institute, 2 Yauzskaya Alley, Moscow, 107564, Russia. Electronic address: [email protected].
⁶ Central Tuberculosis Research Institute, 2 Yauzskaya Alley, Moscow, 107564, Russia. Electronic address: [email protected].
⁷ Central Tuberculosis Research Institute, 2 Yauzskaya Alley, Moscow, 107564, Russia. Electronic address: [email protected].
⁸ Engelhardt Institute of Molecular Biology of the Russian Academy of Sciences, 32 Vavilov St., Moscow, 119991, Russia. Electronic address: [email protected].
⁹ Engelhardt Institute of Molecular Biology of the Russian Academy of Sciences, 32 Vavilov St., Moscow, 119991, Russia. Electronic address: [email protected].
¹⁰ Engelhardt Institute of Molecular Biology of the Russian Academy of Sciences, 32 Vavilov St., Moscow, 119991, Russia. Electronic address: [email protected].

PMID: 32147512
DOI: 10.1016/j.biochi.2020.03.004

Abstract

The data of transmission electron microscopy (TEM) on morphology of M. tuberculosis H37Rv bacterial cells treated with four analogues of pyrimidine nucleosides with different substituents at 5 position of base are presented. We showed that the growth of M. tuberculosis H37Rv cells effectively inhibited by each of these compounds. This process is accompanied with the accumulation of lipid intracellular vacuole-like inclusions in the cells, appearance of deep protrusions and indentations on the surface, partial and/or complete destruction of the three-layered cell envelope. The exact molecular mechanism of action of 5-substituted pyrimidine nucleosides on M. tuberculosis cells remains to be proved. However, one can suggest that mechanism of action for these compounds is related either to their direct interactions with bacteria cell walls or to interactions with enzymes participating in the process of cell wall formation.

Keywords: Antibacterial activity; M. tuberculosis; Nucleoside analogues.

MeSH terms

Microscopy, Electron, Transmission
Mycobacterium tuberculosis* / drug effects
Mycobacterium tuberculosis* / growth & development
Mycobacterium tuberculosis* / ultrastructure
Pyrimidine Nucleosides / pharmacology*

Substances

Pyrimidine Nucleosides