The Inactivation of LPS Biosynthesis Genes in E. coli Cells Leads to Oxidative Stress.

Autor: Seregina TA; Engelhardt Institute of Molecular Biology, Russian Academy of Science, 119991 Moscow, Russia., Petrushanko IY; Engelhardt Institute of Molecular Biology, Russian Academy of Science, 119991 Moscow, Russia., Shakulov RS; Engelhardt Institute of Molecular Biology, Russian Academy of Science, 119991 Moscow, Russia., Zaripov PI; Engelhardt Institute of Molecular Biology, Russian Academy of Science, 119991 Moscow, Russia., Makarov AA; Engelhardt Institute of Molecular Biology, Russian Academy of Science, 119991 Moscow, Russia., Mitkevich VA; Engelhardt Institute of Molecular Biology, Russian Academy of Science, 119991 Moscow, Russia., Mironov AS; Engelhardt Institute of Molecular Biology, Russian Academy of Science, 119991 Moscow, Russia.
Jazyk: angličtina
Zdroj: Cells [Cells] 2022 Aug 27; Vol. 11 (17). Date of Electronic Publication: 2022 Aug 27.
DOI: 10.3390/cells11172667
Abstrakt: Impaired lipopolysaccharide biosynthesis in Gram-negative bacteria results in the "deep rough" phenotype, which is characterized by increased sensitivity of cells to various hydrophobic compounds, including antibiotics novobiocin, actinomycin D, erythromycin, etc. The present study showed that E. coli mutants carrying deletions of the ADP-heptose biosynthesis genes became hypersensitive to a wide range of antibacterial drugs: DNA gyrase inhibitors, protein biosynthesis inhibitors (aminoglycosides, tetracycline), RNA polymerase inhibitors (rifampicin), and β-lactams (carbenicillin). In addition, it was found that inactivation of the gmhA , hldE , rfaD , and waaC genes led to dramatic changes in the redox status of cells: a decrease in the pool of reducing NADPH and ATP equivalents, the concentration of intracellular cysteine, a change in thiol homeostasis, and a deficiency in the formation of hydrogen sulfide. In "deep rough" mutants, intensive formation of reactive oxygen species was observed, which, along with a lack of reducing agents, such as reactive sulfur species or NADPH, leads to oxidative stress and an increase in the number of dead cells in the population. Within the framework of modern ideas about the role of oxidative stress as a universal mechanism of the bactericidal action of antibiotics, inhibition of the enzymes of ADP-heptose biosynthesis is a promising direction for increasing the effectiveness of existing antibiotics and solving the problem of multidrug resistance.
Databáze: MEDLINE
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