Cloning of a DNA region of Actinoplanes teichomyceticus conferring teicoplanin resistance

Abstract

Teicoplanin is a glycopeptide antibiotic, produced by Actinoplanes teichomyceticus, active against Gram positive bacteria and recently introduced into clinical practice. It blocks cell wall biosynthesis by inhibiting peptidoglycan polymerization. The mechanism(s) of resistance of the producer strains of this class of antibiotics have not yet been characterized. We have constructed a genomic bank of A. teichomyceticus in Streptomyces lividans. A clone from this bank, pTR168, was able to confer resistance to teicoplanin on its sensitive host. The restriction map of plasmid pTR 168 and the hybridization pattern to A. teichomyceticus DNA were determined; we have also studied the mechanism of this resistance which seems correlated with a reduced binding of the antibiotic to the cell wall.

Current perspectives on glycopeptide resistance

“…A vanA probe also failed to hybridize with DNA from Amycolatopsis orientalis ATCC 19795 or Actinoplanes teichomyceticus ATCC 31211, which produce vancomycin and teicoplanin, respectively (98). Cloning and sequencing of the teicoplanin resistance gene of A. teichomyceticus have confirmed that there is no nucleotide or amino acid homology with vanA or its product (263,355). It therefore appears unlikely that the van cluster has originated in these organisms.…”