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

Abstract

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.

Exploring the Potential of a Genome-Reduced Escherichia coli Strain for Plasmid DNA Production

“…We hypothesize that the changes in membrane permeability in our strain, resulting from the genome reduction, contribute to its increased sensitivity to antibiotics. This hypothesis is also supported by a previous study [31]. This characteristic provides more advantages in our strain as a platform for plasmid production.…”

Enhancing osteogenic differentiation of MC3T3-E1 cells during inflammation using UPPE/β-TCP/TTC composites via the Wnt/β-catenin pathway

“…TTC is a commonly used antibiotic in clinical practice. 36 Besides its antibacterial properties, TTC exhibits various special effects including anti-inflammatory, anti-ulcer, and promoting bone tissue regeneration. 37 Although TTC, a fermentation product of the Streptomyces aureofaciens bacteria discovered as early as 1948, research on TTC has continued to the present day.…”

Antimicrobial Activity and Phytochemical Characterization of Baccharis concava Pers., a Native Plant of the Central Chilean Coast

“…Therefore, we speculate that active molecules in the tested extract poorly penetrate the bacterial envelope of Gram-negatives with an intact LPS. Moreover, new evidence indicates that this kind of mutant accumulates oxidative species, which in turn may facilitate killing by antimicrobial agents [21].…”