Diminazene aceturate: an antibacterial agent for Shiga-toxin-producing <em>Escherichia coli </em>O157:H7

Abstract

The aim of this study was to investigate the bacteriostatic and bactericidal effects of diminazene aceturate (DA) against five strains of pathogenic bacteria and two strains of nonpathogenic bacteria. The results showed that 5 μg/mL of DA suppressed the growth of pathogenic Escherichia coli by as much as 77% compared with the controls. Enterohemorrhagic E. coli EDL933 (an E. coli O157:H7 strain) was the most sensitive to DA with a minimum inhibitory concentration of 20 μg/mL. Additional investigations showed that DA induced the highest level of intracellular reactive oxygen species in EDL933. A positive correlation between the reactive oxygen species levels and DA concentration was demonstrated. DA (5 μg/mL) was also a potent uncoupler, inducing a stationary phase collapse (70%–75%) in both strains of E. coli O157:H7. Further investigation showed that the collapse was due to the NaCl:DA ratio in the broth and was potassium ion dependent. A protease screening assay was conducted to elucidate the underlying mechanism. It was found that at neutral pH, the hydrolysis of H-Asp-pNA increased by a factor of 2–3 in the presence of DA, implying that DA causes dysregulation of the proton motive force and a decrease in cellular pH. Finally, a commercial verotoxin test showed that DA did not significantly increase toxin production in EDL933 and was a suitable antibacterial agent for Shiga-toxin-producing E. coli.

Dissociation kinetics of small-molecule inhibitors in Escherichia coli is coupled to physiological state of cells

“…Our findings collectively demonstrate the co-existence of two subpopulations with distinct unbinding kinetics and growth rates, supporting our hypothesis. We next repeated this single-cell experiment with two commercially available drugs that target DNA and exhibit anti-microbial activities, netropsin and berenil 56 – 58 . We again observed two distinct subpopulations (Supplementary Video 2 and 3 ).…”

N-(Isobutyl)-3,4-methylenedioxy Cinnamoyl Amide

“…brucei while at the same time producing little or no effects on normal cells. This result is interesting, given that the drug diminazene aceturate which is used to treat bacteria and protozoan infections in animals is significantly toxic [27][28][29][30].…”

A review on therapeutic activities of diminazene aceturate

“…A study investigated the bacteriostatic and bactericidal effects of diminazene aceturate (DA) against five strains of pathogenic bacteria (Escherichia coli (E.coli), O157:H7) and two strains of non-pathogenic bacteria (commensal E. coli) (Wu et al, 2016). The results showed the ability of DA to inhibit or suppress the growth of E. coli O157:H7 via reactive oxygen species (ROS) accumulation (Wu et al, 2016). Increase in intracellular ROS levels decrease extracellular peroxidase activity making the host bacteria more susceptible to external ROS attack.…”

“…(8) It can be used to treat blood fluke or schistomiasis (De brito et al, 2020) (9) Diminazene aceturate has antibacterial properties against Escherichia coli (Wu et al, 2016).…”