Oncocin derivative Onc72 is highly active against Escherichia coli in a systemic septicaemia infection mouse model.
OBJECTIVE
The antimicrobial oncocin derivative Onc72 is highly active against a number of Gram-negative bacteria, including resistant strains. Here we study its toxicity and efficacy in a lethal mouse infection model.


METHODS
In an acute toxicity study, purified Onc72 was administered to NMRI mice in four consecutive injections within a period of 24 h as an intraperitoneal bolus. The animals' behaviour was monitored for 5 days, before several organs were examined by histopathology. A lethal Escherichia coli infection model was established and the efficacy of Onc72 was evaluated for different peptide doses considering the survival rates of each dose group and the bacterial counts in blood, lavage and organs.


RESULTS
Intraperitoneal bolus injections with single doses of 20 or 40 mg of Onc72 per kg of body weight did not result in any abnormal animal behaviour. No mouse became moribund or died within the studied period. Histopathological examinations revealed no toxic effects. When infected with E. coli at a lethal dose, none of the untreated animals survived the next 24 h, whereas all animals treated three times with Onc72 at doses of ≥5 mg/kg survived the observation period of 5 days. No bacteria were detected in the blood of treated animals after day 5 post-infection. The effective dose (ED(50)) was ∼2 mg/kg.


CONCLUSIONS
No toxic effects were observed for Onc72 within the studied dose range up to 40 mg/kg, indicating a safety margin of >20.
Institute of Bioanalytical Chemistry, Faculty of Chemistry and Mineralogy, Universität Leipzig, Leipzig, Germany.
Daniel
D
Knappe
Stefanie
S
Fritsche
Gottfried
G
Alber
Gabriele
G
Köhler
Ralf
R
Hoffmann
Uwe
U
Müller
D000825:Animal Structures / Q000473:pathology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000009:adverse effects; D023181:Antimicrobial Cationic Peptides / Q000008:administration & dosage* / Q000009:adverse effects; D004195:Disease Models, Animal; D004926:Escherichia coli / Q000187:drug effects*; D004927:Escherichia coli Infections / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D005260:Female; D007274:Injections, Intraperitoneal; D051379:Mice; D018805:Sepsis / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D016019:Survival Analysis; D016896:Treatment Outcome
D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; C551620:oncocin