SPECIFICITY OF INDUCTION OF GLYCOPEPTIDE RESISTANCE GENES IN ENTEROCOCCUS-FAECALIS

Regulation of VanA- and VanB-type glycopeptide resistance in enterococ ci is mediated by related two-component regulatory systems (VanR-VanS add VanR(B)-VanS(B)). The transglycosylase inhibitors vancomycin, teic oplanin, and moenomycin induced synthesis of the VanX D,D-dipeptidase in a VanA-type Enterococcus faecalis harboring transposon Tn1546. Inhi bitors of reactions immediately preceding (ramoplanin) or following (p enicillin G and bacitracin) transglycosylation were not inducers, Thes e results identify accumulation of membrane-bound lipid intermediate I I as a potential signal for induction of VanA-type resistance. In E. f aecalis BM4281 harboring a wild vanB genetic element, D,D-dipeptidase synthesis was only inducible by vancomycin, Induction of the productio n of the VanB ligase by vancomycin was required for growth of a vancom ycin-dependent derivative of BM4281, since introduction of a plasmid c oding for constitutive synthesis of the VanA ligase eliminated the req uirement of glycopeptide for growth. Both vancomycin and teicoplanin w ere able to induce D,D-dipeptidase synthesis in BM4281 derivatives tha t were vancomycin and teicoplanin resistant or vancomycin and teicopla nin dependent, Acquisition of teicoplanin resistance in the latter typ es of strains was due to alteration in induction specificity associate d with an increase in the sensitivity of the regulatory system to vanc omycin. Thus, the wild VanR(B)-VanS(B) system is unable or not sensiti ve enough to sense teicoplanin, although mutations can lead to recogni tion of this antibiotic.