Regulation of the erm(C) Gene in Staphylococci from Reservoir with Different Usage of Macrolides

A high prevalence of macrolide resistant isolates has been found among staphylococci isolated from animals (4). The erm(C) gene is the most common gene encoding macrolide resistance in staphylococci (8). It is well known that expression of the erm(C) gene is normally regulated by formation of hairpin structures upstream for the erm(C) gene (5,9) rendering the start codon of erm(C) gene non-accessible. Only 14and 15-membered macrolides like erythromycin can induce expression of the gene and induce resistance while 16-membered macrolides cannot activate expression of erm (C) (7). If deletions from 16 to 116 bp occur in the regulatory area, expression of the erm(C) gene becomes constitutive (10). Constitutive expressed erm(C) genes give resistance not only to 14-and 15-membered macrolides, like erythromycin, but also to 16-membered macrolides like spiramycin, tylosin and streptogramin B (6). Deletions are believed to be the result of high concentration of non-inducible macrolides like tylosin in the environment, selecting for constitutive expression of the macrolide resistance. In the presence of macrolides, like tylosin, this could give staphylococci with constitutive expressed erm(C) a selective advantage not only to sensitive staphylococci but also to staphylococci containing regulated erm(C) genes. In this article we have investigated the ratio of regulated and constitutive expressed erm(C) genes in human and animal reservoirs (cattle and pigs) with differences in uses of the 16-membered macrolide tylosin. Large amounts of the macrolide tylosin have been used for pig production in Denmark for growth promotion and therapy (1). In 1996 68,350 kg of tylosin was used for growth promotion and 1,350 kg for therapy. No macrolides have been used for growth promotion for cattle but spiramycin and tylosin have been used therapeutically for treatment of mastitis (3). A total of 644 kg macrolides, primarily tylosin, was used for cattle in 1996 in Denmark. Local variations in treatment strategies exist depending on the choice of the veterinarian but due to the used strain collection this effect will be minimal. At the same time 5,934 kg of penicillin was used (Erik Jacobsen, personal communication). The usage of macrolides for treatment of infections in human in general practice constitutes approximately 20-25 percent of the total usage of antibiotics in humans. However, in human medicine 16-membered macrolides are not used. The macrolides used in human medicine in Denmark are primarily erythromycin (14membered) and azithromycin (2). A total of 185 macrolide resistant staphylococci Acta vet. scand. 2005, 46, 163-166.