GENETICS OF GLYCOPEPTIDE RESISTANCE IN ENTEROCOCCI

Glycopeptide resistance in enterococci is phenotypically and genotypic ally heterogeneous, The genes responsible for inducible resistance to high levels of vancomycin and teicoplanin (VanA phenotype) are carried by the 10,851-bp Tn1546 transposon, Transposition of Tn1546 into self -transferable plasmids and subsequent transfer by conjugation appears to be responsible for the dissemination of this type of resistance, Ni ne polypeptides are encoded by Tn1546 that belong to five functional g roups: transposition functions (ORF1 and ORF2), regulation of resistan ce gene expression (VanR and VanS), synthesis of depsipeptide D-Ala-D- lactate (VanH and VanA), hydrolysis of D-Ala-D-Ala-containing peptidog lycan precursors (VanX and VanY), and low-level teicoplanin resistance (VanZ), VanB-type resistance (various levels of resistance to vancomy cin and susceptibility to teicoplanin) is also due to production of D- Ala-D-Lac, The VanB ligase of VanB-type strains is structurally and fu nctionally similar to VanA, The vanB gene was found on composite trans poson Tn1547, which, in turn, was part of larger conjugative chromosom ally located elements (90 to 250 kb), In contrast to acquired VanA- an d VanB-type resistance, VanC-type resistance (low level of resistance to vancomycin and susceptibility to teicoplanin) is an intrinsic prope rty of motile enterococci, Resistance in these species is due to synth esis of dipeptide D-Ala-D-Ser by VanC ligases leading to production of cell wall precursors with reduced vancomycin affinity.