Introduction. Plasmid-mediated resistance to the glyco-peptide antibiotics vancomycin and teicoplanin was first detected in 1986 (35, 53). It was rapidly shown that glyco-peptide-resistant enterococci had a broad geographical dis-tribution and were phenotypically and genotypically heterogeneous (Table 1). Strains displaying the VanA resistance phenotype have been studied extensively, leading to the first elucidation of a mechanism of resistance to glycopeptides and to an insight into the regulation and mode of dissemination of the corresponding genes. We review the experimental approaches used to characterize the molecular basis of VanA resistance and briefly discuss the similarities and differences between the VanA phenotype and other phenotypes. The clinical implications (19, 31) and the mechanism (59) of glycopeptide resistance have recently been reviewed. The VanA phenotpe. Inducible resistance to high levels of vancomycin and teicoplanin defines the VanA phenotype (18). This type of resistance reduces the activities of all glycopeptides to various extents, but there is no cross-resistance with other cell wall inhibitors (35, 40). Vancomycin induces the synthesis of two proteins that are readily detectable in enterococcal membrane fractions: a 39-kDa protein (5, 41, 50), which was identified as the VanA ligase necessary for cell wall synthesis in the presence of glyco-peptides (21), anda D, D-carboxypeptidase (4) that isnot required for resistance (7). High-level resistance to glyco-peptides is generally transferable to susceptible enterococci by conjugation and was shown, at least in certain strains, to be mediated by self-transferable plasmids (20, 28, 36, 41, 43, 50, 53). It has recently been shown (9) that the genes necessary and sufficient for expression of the VanA phenotype are carried by a transposon designated TnI546. Dissem-ination of this transposon appears to be responsible for the spread of high-level glycopeptide resistance among clinical isolates of enterococci (9).

Overview of Tn1546. Originally detected on plasmid pIP816 from Enterococcus faecium BM4147 (9, 35), TnJS46 consists of 10,851 bp and encodes nine polypeptides (Fig. 1) that can be assigned to four functional groups (7-9): trans-position functions (open reading frames [ORFs] ORF1 and ORF2), regulation of vancomycin resistance genes (VanR and VanS), resistance to glycopeptides by production of depsipeptides (VanH, VanA, and VanX), andaccessory proteins that maybe involved in peptidoglycan synthesis,