INDUCTION OF VANA VANCOMYCIN RESISTANCE GENES IN ENTEROCOCCUS-FAECALIS - USE OF A PROMOTER FUSION TO EVALUATE GLYCOPEPTIDE AND NONGLYCOPEPTIDE INDUCTION SIGNALS

To characterize induction of VanA resistance a plasmid was constructed in which the gene for firefly luciferase lucA was placed under the co ntrol of the promoter for the VanA resistance genes, the vanH promoter . This system afforded convenient quantitative measurement of inductio n of the VanA genes. Glycopeptide antibiotics and antibiotics represen ting 19 different mechanisms of action were evaluated for their abilit y to induce. Antibiotics that acted as inducers were all inhibitors of late steps of peptidoglycan synthesis. These included moenomycin, bac itracin, tunicamycin, ramoplanin and glycopeptides, but not penicillin or other beta-lactam antibiotics. Glycopeptide antibiotics were the m ost potent inducers. Both glycopeptides with little or no antimicrobia l activity and semisynthetic glycopeptides active against VanA resista nt enterococci were inducers. Overall, results suggest that an inducti on response may involve both an internal signal, such as precursor acc umulation, and the glycopeptide molecule itself as a signal. The syste m may be useful as a screen for new antimicrobial agents.