title: Diminazene aceturate: an antibacterial agent for Shiga-toxin-producingEscherichia coliO157: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 pathogenicEscherichia coliby as much as 77% compared with the controls. EnterohemorrhagicE. coliEDL933 (anE. coliO157: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 ofE. coliO157: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-producingE. coli.
authors: Department of BioNano Technology, Gachon BioNano Research Institute, Gachon University, Seongnam-si.
authors: Si-Ying
authors: SY
authors: Wu
authors: Department of BioNano Technology, Gachon BioNano Research Institute, Gachon University, Seongnam-si.
authors: Gil-Yong
authors: GY
authors: Park
authors: Seoul National University Bundang Hospital, Gyeonggi-do, Republic of Korea.
authors: So-Hee
authors: SH
authors: Kim
authors: Department of BioNano Technology, Gachon BioNano Research Institute, Gachon University, Seongnam-si.
authors: John
authors: J
authors: Hulme
authors: Department of BioNano Technology, Gachon BioNano Research Institute, Gachon University, Seongnam-si.
authors: Seong Soo A
authors: SS
authors: An
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D004133:Diminazene / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D019453:Escherichia coli O157 / Q000737:chemistry / Q000187:drug effects*; D057166:High-Throughput Screening Assays; D010447:Peptide Hydrolases / Q000737:chemistry*; D022621:Shiga Toxin / Q000037:antagonists & inhibitors*; D022603:Shiga Toxins / Q000009:adverse effects* / Q000737:chemistry
chemical_list: D000900:Anti-Bacterial Agents; D022603:Shiga Toxins; D022621:Shiga Toxin; D010447:Peptide Hydrolases; C003915:diminazene aceturate; D004133:Diminazene
keywords: Berenil©; E. coli O157; ROS; enterohemorrhagic; protease; reversible