Oncocins and apidaecins are short
proline-rich
antimicrobial peptides (PrAMPs) representing novel
antibiotic drug lead compounds that kill bacteria after internalization and inhibition of intracellular targets (e.g. 70S ribosome and DnaK).
Oncocin Onc72 is highly active against Gram-negative bacteria in vitro and in vivo protecting mice in systemic
infection models with Escherichia coli and KPC-producing Klebsiella pneumoniae. Here we studied its efficacy in a murine thigh
infection model using
meropenem as
antibiotic comparator that had a 44-fold higher molar in vitro activity than Onc72. Male CD1 mice were rendered neutropenic using
cyclophosphamide for four days before intramuscular
infection with K. pneumoniae ATCC 43816. After 75 min
oncocin Onc72 or the
antibiotic comparator
meropenem were administered subcutaneously with 100 mg (43 µmol) and 25 mg (65 µmol) per kg of
body weight, respectively, six times every 75 min. Onc72 and
meropenem administered subcutaneously reduced the thigh tissue burden of K. pneumoniae ATCC 43816 in neutropenic mice significantly by 4.14 and 4.65 a log10 cfu/g, respectively. The bacterial counts were ∼0.5 and ∼1 log10 below the pre-treatment burden, respectively, indicating bactericidal effects for both compounds. Thus, Onc72 was as efficacious as
meropenem in vivo despite its much lower in vitro activity determined according to CLSI standard antimicrobial activity tests.