Genetic Determinants of Tetracycline Resistance and their Effect on Tetracycline and Glycylcycline Antibiotics

Tetracycline class antibiotics have been a hallmark in terms of safety profile and spectrum of activity for nearly 60 years. Multiple resistance mechanisms have evolved to counter the tetracyclines with both of the chief mechanisms - efflux and ribosomal protection - widely spread in Gram-positive and Gram-negative organisms. The utility of the tetracyclines as growth promoters in domesticated food animals as well as for pest control in aquaculture and horticulture has resulted in the dissemination of tetracycline resistance determinants in the environment, which may act as a reservoir for resistance genes. Focused chemistry efforts to develop tetracycline derivatives not subject to the efflux and ribosomal protection mechanism resulted in the discovery of tigecycline, the first in class glycylcycline antibiotic. Tigecycline has successfully reclaimed the spectrum, safety and efficacy of the tetracyclines.