Glycopeptide resistance determinants from the teicoplanin producer Actinoplanes teichomyceticus.
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.
Serina
Stefania
S
Vicuron Pharmaceuticals - Microbial Technologies, via R. Lepetit 34, 21040 Gerenzano, Italy.
Radice
Francesca
F
Maffioli
Sonia
S
Donadio
Stefano
S
Sosio
Margherita
M
D000900:Anti-Bacterial Agents / Q000096:biosynthesis*; D004926:Escherichia coli / Q000235:genetics; D008848:Micromonosporaceae / Q000235:genetics* / Q000378:metabolism; D010453:Peptide Synthases / Q000235:genetics* / Q000378:metabolism; D048372:Streptomyces coelicolor / Q000235:genetics; D017334:Teicoplanin / Q000096:biosynthesis*; D013696:Temperature; D020713:Vancomycin Resistance / Q000235:genetics*
D000900:Anti-Bacterial Agents; D017334:Teicoplanin; D010453:Peptide Synthases; C060628:UDP-N-acetylmuramoylalanyl-D-glutamyllysine-D-alanyl-D-alanine ligase