Telavancin’s interactions with the bacterial cell membrane

Evaluation of: Lunde CS, Hartouni SR, Janc JW, Mammen M, Humphrey PP, Benton BM: Telavancin disrupts the functional integrity of the bacterial membrane through targeted interaction with the cell wall precursor lipid II. Antimicrob. Agents Chemother. 53, 3375-3383 (2009). It has been previously demonstrated that telavancin has a dual mechanism of action: inhibition of the transglycosylation process of peptidoglycan cell wall synthesis by the formation of a complex with the D-alanyl-D-alanine precursors; and depolarization of the bacterial membrane. In this article the mechanism by which telavancin disrupts the bacterial cell membrane was studied by Lunde and colleagues using a variety of Staphylococcus aureus strains. The authors demonstrated that telavancin-induced depolarization requires both the presence of lipid II as well as an interaction between telavancin and D-alanyl-D-alanine residues. The authors were also able to show that telavancin's depolarization effect on membrane potential occurs in diverse S. aureus strains including those with decreased susceptibility to vancomycin and daptomycin. This study takes a significant step forward in our understanding of the concentration-dependent bactericidal activity of telavancin, a drug recently approved for use in skin and skin structure infections caused by Gram-positive cocci.