Look and Outlook on Enzyme-Mediated Macrolide Resistance

Since their discovery in the early 1950s, macrolide antibiotics have been used in both agriculture and medicine. Specifically, macrolides such as erythromycin and azithromycin have found use as substitutes for beta-lactam antibiotics in patients with penicillin allergies. Given the extensive use of this class of antibiotics it is no surprise that resistance has spread among pathogenic bacteria. In these bacteria different mechanisms of resistance have been observed. Frequently observed are alterations in the target of macrolides, i.e., the ribosome, as well as upregulation of efflux pumps. However, drug modification is also increasingly observed. Two classes of enzymes have been implicated in macrolide detoxification: macrolide phosphotransferases and macrolide esterases. In this review, we present a comprehensive overview on what is known about macrolide resistance with an emphasis on the macrolide phosphotransferase and esterase enzymes. Furthermore, we explore how this information can assist in addressing resistance to macrolide antibiotics.