Aminoglycoside antibiotics resistance, enzymatic mechanism

A variety of enzymatic mechanisms for antibiotic resistance are known. Hydrolysis of the lactam rings of /3-lactams, cephalosporins, and carbapenams destroys their ability to inhibit transpeptidases that cross-link peptidoglycan in bacterial cell walls. Modification of aminoglycoside antibiotics by acetylation, phosphorylation, or adenylation interferes with their ability to bind to the 16S subunit of the ribosome. Streptogramin activity can be destroyed by acetylation or by an elimination reaction that opens the lactone ring. The enzymes responsible for these detoxification reactions evolved in response to naturally occurring antibiotics, but are easily adapted to modify semisynthetic and completely synthetic antibiotics. For example, only a few point mutations are needed to enhance the ability of TEM /3-lactamases to hydrolyze third-generation cephalosporins such as cefotaxime and ceftazidime. ... 

An intervening chapter delineates the enzymatic basis for the bacterial resistance to five classes of antibiotics the /3-lactams (e.g., penicillin), the glycopeptides (e.g., vancomycin), the aminoglycosides (e.g., streptomycin), the macrolides (e.g., erythromycin), and the quinolones (e.g., ciprofloxacin). The classes represent the major antibiotics used clinically today. Starting with the /3-lactams and ending with the fluoroquinolones, the authors discuss the mechanisms and molecular basis for resistance, and show how resistance is not a matter of if, but when. 

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