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Specificity of Induction of the vanA and vanB Operons in Vancomycin-Resistant Enterococci by Telavancin▿ †

By Craig M. Hill, Kevin M. Krause, Stacey R. Lewis, Johanne Blais, Bret M. Benton, Mathai Mammen, Patrick P. Humphrey, Alfred Kinana and James W. Janc

Abstract

Telavancin is a bactericidal, semisynthetic lipoglycopeptide indicated in the United States for the treatment of complicated skin and skin structure infections caused by susceptible Gram-positive bacteria and is under investigation as a once-daily treatment for nosocomial pneumonia. The related vanA and vanB gene clusters mediate acquired resistance to glycopeptides in enterococci by remodeling the dipeptide termini of peptidoglycan precursors from d-alanyl-d-alanine (d-Ala-d-Ala) to d-alanyl-d-lactate (d-Ala-d-Lac). In this study, we assessed the ability of telavancin to induce the expression of van genes in VanA- and VanB-type strains of vancomycin-resistant enterococci. Vancomycin, teicoplanin, and telavancin efficiently induced VanX activity in VanA-type strains, while VanX activity in VanB-type isolates was inducible by vancomycin but not by teicoplanin or telavancin. In VanA-type strains treated with vancomycin or telavancin, high levels of d-Ala-d-Lac-containing pentadepsipeptide were measured, while d-Ala-d-Ala pentapeptide was present at very low levels or not detected at all. In VanB-type strains, vancomycin but not telavancin induced high levels of pentadepsipeptide, while pentapeptide was not detected. Although vancomycin, teicoplanin, and telavancin induced similar levels of VanX activity in VanA-type strains, these organisms were more sensitive to telavancin, which displayed MIC values that were 32- and 128-fold lower than those of vancomycin and teicoplanin, respectively

Topics: Mechanisms of Resistance
Publisher: American Society for Microbiology (ASM)
OAI identifier: oai:pubmedcentral.nih.gov:2897282
Provided by: PubMed Central
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