Combined bacterial targets: peptidoglycan precursors + 30S ribosomal decoding center and additional ribosomal sites

This composite target represents the multi-faceted mechanism of action of advanced lipoglycopeptide antibiotics, most notably Oritavancin. It encompasses the inhibition of bacterial cell wall synthesis through binding to peptidoglycan precursors like Lipid II and the D-Ala-D-Ala terminus, as well as the disruption of protein synthesis via interaction with the 30S ribosomal decoding center and additional ribosomal sites. By hitting multiple essential bacterial processes simultaneously, drugs targeting this complex exhibit potent bactericidal activity against multidrug-resistant Gram-positive pathogens, including MRSA and VRE. The dual-targeting of the cell wall and the translational machinery helps overcome common resistance mechanisms that affect single-target glycopeptides like vancomycin. Clinically, this target is primarily relevant in the treatment of acute bacterial skin and skin structure infections (ABSSSI).

Other names

Multi-target bacterial cell wall and ribosome complexOritavancin target complexLipid II and 30S ribosome decoding centerPeptidoglycan precursors and ribosomal sites

Inhibition of transglycosylation and transpeptidation by binding to peptidoglycan precursors (Lipid II and D-Ala-D-Ala); disruption of bacterial membrane potential; and inhibition of protein synthesis by binding to the 30S ribosomal decoding center and other ribosomal sites.