ICAAC Lecture

Saturday, September 6 | 10:45 a.m. – 11:45 a.m.

KBush

Beta-Lactamases: Ubiquitous and Formidable

Karen Bush; Indiana Univ., Bloomington, IN

Beta-Lactamases are the major cause for resistance to the beta-lactam antibiotics in Gram-Negative bacteria. These ancient enzymes that are assumed to have originated from the penicillin-binding proteins now include over 1500 unique, naturally-occurring enzymes with a broad spectrum of hydrolytic activity. Among the most infamous of these enzymes are the TEM family of enzymes that was responsible for the loss of single dose penicillin therapy for treatment of gonorrhea in the 1970s and the carbapenemases that have contributed to the loss of empiric beta-lactam therapy to treat serious infections caused by Gram-negative pathogens. Enzymes such as NDM-1 and KPC-3 have become notorious threats by defying our antibiotic armamentarium, as detailed both in the scientific literature and the public media. The widespread influence and impacts of beta-lactamases have driven antibiotic drug discovery over the past five decades, and are responsible for the introduction of some of our most effective antibacterial agents. The close interrelationship between beta-lactam development and beta-lactamase evolution will be explored in some detail.