The Mechanism of Action of the Novel Aminomethylcycline Antibiotic Omadacycline.
Antimicrob Agents Chemother. 2013 Sep 16;
Authors: Draper MP, Weir S, Macone A, Donatelli J, Trieber CA, Tanaka SK, Levy SB
Abstract
Omadacycline is a novel first in class aminomethylcycline with potent activity against important skin and pneumonia pathogens including community-acquired MRSA, ß-hemolytic streptococci, penicillin-resistant S. pneumoniae, H. influenzae, and Legionella. In this work the mechanism of action for omadacycline is further elucidated using a variety of models. Functional assays demonstrate that omadacycline is active against strains expressing the two main forms of tetracycline resistance (efflux and ribosomal protection). Macromolecular synthesis experiments confirm the primary effect of omadacycline is on bacterial protein synthesis, inhibiting protein synthesis with a potency greater than tetracycline. Biophysical studies with isolated ribosomes confirmed that the binding site for omadacycline is similar to that for tetracycline. In addition, unlike tetracycline omadacycline is active in vitro in the presence of the ribosomal protection protein Tet(O).
PMID: 24041885 [PubMed - as supplied by publisher]