STRESS-ACTIVATED EXPRESSION OF A STREPTOMYCES-PRISTINAESPIRALIS MULTIDRUG-RESISTANCE GENE (PTR) IN VARIOUS STREPTOMYCES SPP AND ESCHERICHIA-COLI

A promoter which controls expression of the pristinamycin multidrug re sistance gene (ptr) in Streptomyces pristinaspiralis could be induced by physiological stresses in both Streptomyces spp. and Escherichia co li. In S. pristinaspiralis, the ptr promoter (Pptr) was induced by pri stinamycin I (PI) or pristinamycin II (PII). Streptomyces lividans was adopted as a convenient heterologous host for studies of Pptr regulat ion since it has no known pristinamycin biosynthetic genes. Two key re gulatory features were documented in these studies: many (19 of 70) an tibiotics and chemicals with no common targets or structural features induced the Pptr; induction with PI was most efficient during a transi tion phase when antibiotic biosynthetic genes are switched on. In Stre ptomyces coelicolor, Pptr activity was similarly inducible by PI and n ot dependent on sigma factors HrdA, HrdC, or HrdD. In E. coli, Pptr cl oned in the bifunctional promoter probe vector pIJ2839 was functional and activated upon entry into stationary phase in the absence of exoge nous inducer. Finally, gel-retardation studies demonstrated a Pptr-bin ding protein in S. lividans (where its activity was PI-inducible), S. coelicolor and S. pristinaespiralis. The fact that this activity was n ot detected in E. coli suggested the existence of another regulatory s ystem perhaps also present in Streptomyces.