Open AccessSpecificity of Induction of the vanA and vanB Operons in Vancomycin-Resistant Enterococci by Telavancin
Author(s) -
Craig Hill,
Kevin M. Krause,
Stacey R. Lewis,
Johanne Blais,
Bret M. Benton,
Mathai Mammen,
P. P. A. Humphrey,
Alfred Kinana,
James W. Janc
Publication year - 2010
Publication title -
antimicrobial agents and chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.07
H-Index - 259
eISSN - 1070-6283
pISSN - 0066-4804
DOI - 10.1128/aac.01737-09
Subject(s) - teicoplanin , vancomycin , microbiology and biotechnology , glycopeptide , biology , glycopeptide antibiotic , enterococcus , antibiotics , bacteria , staphylococcus aureus , genetics
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 relatedvanA andvanB gene clusters mediate acquired resistance to glycopeptides in enterococci by remodeling the dipeptide termini of peptidoglycan precursors fromd -alanyl-d -alanine (d -Ala-d -Ala) tod -alanyl-d -lactate (d -Ala-d -Lac). In this study, we assessed the ability of telavancin to induce the expression ofvan 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 ofd -Ala-d -Lac-containing pentadepsipeptide were measured, whiled -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.