Specificity of Induction of Glycopeptide Antibiotic Resistance in the Producing Actinomycetes.

Glycopeptide antibiotics are drugs of last resort for treating severe infections caused by Gram-positive pathogens. It is widely believed that glycopeptide-resistance determinants ( genes) are ultimately derived from the producing actinomycetes. We hereby investigated the relationship between the antimicrobial activity of vancomycin and teicoplanins and their differential ability to induce gene expression in —the producer of teicoplanin—and —the producer of the teicoplanin-like A40926. As a control, we used the well-characterized resistance model . The enzyme activities of a cytoplasmic-soluble d,d-dipeptidase and of a membrane-associated d,d-carboxypeptidase (corresponding to VanX and VanY respectively) involved in resistant cell wall remodeling were measured in the actinomycetes grown in the presence or absence of subinhibitory concentrations of vancomycin, teicoplanin, and A40926. Results indicated that actinomycetes possess diverse self-resistance mechanisms, and that each of them responds differently to glycopeptide induction. Gene swapping among teicoplanins-producing actinomycetes indicated that cross-talking is possible and provides useful information for predicting the evolution of future resistance gene combinations emerging in pathogens.