A novel mechanism of antibiotic resistance: study of the complex state of peptides with bacterial Staphylococcus aureus ribosomes

Abstract

Two antibiotic resistance peptides, the E-peptide (MRLFV) and the K-peptide (MRFFV) conferring macrolide and ketolide resistance, respectively, were studied in the complex state with bacterial Staphylococcus aureus ribosomes after a conformational analysis by NMR spectroscopy and molecular modeling of the unbound molecules. T2 (CPMG) measurements were used to characterize equilibrium binding of antibiotic resistance peptides to bacterial ribosomes. Additionally, interactions of antibiotic resistance peptide to ribosomes were investigated using two-dimensional transferred nuclear Overhauser effect spectroscopy (TRNOESY), resulting in bound structures compatible with the experimental NMR data.