Open AccessGlycopeptide resistance determinants from the teicoplanin producer Actinoplanes teichomyceticus
Author(s) -
Serina Stefania,
Radice Francesca,
Maffioli Sonia,
Donadio Stefano,
Sosio Margherita
Publication year - 2004
Publication title -
fems microbiology letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.899
H-Index - 151
eISSN - 1574-6968
pISSN - 0378-1097
DOI - 10.1016/j.femsle.2004.09.017
Subject(s) - teicoplanin , glycopeptide , streptomyces coelicolor , glycopeptide antibiotic , microbiology and biotechnology , depsipeptide , biology , gene cluster , peptidoglycan , mutant , bacteria , gene , vancomycin , biochemistry , antibiotics , genetics , staphylococcus aureus
In enterococci and other pathogenic bacteria, high‐level resistance to vancomycin and other glycopeptide antibiotics requires the action of the van genes, which direct the synthesis of peptidoglycan terminating in the depsipeptide d ‐alanyl‐ d ‐lactate, in place of the usual d ‐Ala‐ d ‐Ala. The Actinoplanes teichomyceticus tcp cluster, devoted to the biosynthesis of the glycopeptide antibiotic teicoplanin, contains van genes associated to a murF ‐like sequence ( murF2 ). We show that A. teichomyceticus contains also a house‐keeping murF1 gene, capable of complementing a temperature sensitive Escherichia coli murF mutant. MurF1, expressed in Streptomyces lividans , can catalyze the addition of either d ‐Ala‐ d ‐Ala or d ‐Ala‐ d ‐Lac to the UDP‐ N ‐acetyl‐muramyl‐ l ‐Ala‐ d ‐Glu‐ d ‐Lys. However, similarly expressed MurF2 shows a small enzymatic activity only with d ‐Ala‐ d ‐lactate. Introduction of a single copy of the entire set of van genes confers resistance to teicoplanin‐type glycopeptides to S. coelicolor .