CrpP Is Not a Fluoroquinolone-Inactivating Enzyme
Haley L. Zubyk, Gerard D. Wright
Abstract
Enzyme-mediated antibiotic inactivation is a common mechanism of drug resistance in bacteria (1). The genes encoding these resistance proteins are frequently associated with mobile elements, making them particularly concerning due to their propensity for horizontal transfer through bacterial populations. Given the specificity of enzymes for their substrates, which has often coevolved with antibiotic production over millennia (2), it is not surprising that natural-product antibiotics and their semisynthetic derivatives are particularly vulnerable to enzymatic inactivation. Various hydrolases (β-lactams), kinases (aminoglycosides and macrolides), nucleotidyltransferases (lincosamides and aminoglycosides), acyltransferases (chloramphenicol and aminoglycosides), oxygenases (tetracyclines and rifamycins), and many others are known. In contrast, enzyme-mediated inactivation of synthetic antibiotics is rare. Examples include monooxygenase-mediated inactivation of sulfonamides by soil bacteria (3) and coopting of an aminoglycoside acetyltransferase, AAC(6′)-Ib-cr, for the modification of fluoroquinolone antibiotics containing a piperazine moiety with a free secondary amine, such as ciprofloxacin (CIP) and norfloxacin (4, 5).