Beta-lactamases: clinical impact and epidemiology

Published on December 31, 2009 Updated on November 30, 2015   38 min

Other Talks in the Category: Clinical Medicine

0:00
My name is Sebastian Amyes, and I'm professor of antimicrobial chemotherapy at the University of Edinburgh in Scotland in the north of the United Kingdom. I and my colleagues have spent much of our careers looking at beta-lactamases, both their structure and function, and putting this into context with clinical impact and epidemiology. In this presentation I shall talk about the impact of beta-lactamases and outline some of the most important beta-lactamases that we're having to deal with in the clinical situation today.
0:33
Most of the beta-lactamases I'm going to talk about are in Gram-negative bacteria. There are, of course, beta-lactamases in Gram-positive bacteria and they have caused problems clinically, but largely they are overcome by new drugs such as methicillin and the newer cephalosporins. There are more than 2,000 beta-lactamases reported since their first discovery by Abraham and Chain in 1940. And many of these are of clinical importance. The ones that I'm particularly going to talk about are those that cause problems at the moment, those that confer resistance to the cephalosporins. The transferable class C beta-lactamases and what we know as extended-spectrum beta-lactamases. Also, I'm going to talk about those that confer resistance to the carbapenems. The transferable class B and transferable class D beta-lactamases, but we would discuss these in more detail later on.
1:32
First, we must look at the action of a beta-lactamase. And on the left hand side of this slide, you see the structure of amoxicillin with the beta-lactam ring. It's a four-membered planar ring at the tip of the arrow. The beta-lactamase hydrolyzes the carbon nitrogen bond at the bottom of that ring, so that the molecule can rotate around the opposite bond. Once that ring is broken, the molecule is no longer active. And so important is this as a defense mechanism in bacteria that it is an example of convergent evolution. There are four classes of beta-lactamases which can do this. Three of them, A, C and D have a serine at the active site and B usually has a zinc ion at the active site. A, C and D are probably very, very distantly related to one another, but they now share almost no common primary structure.
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Beta-lactamases: clinical impact and epidemiology

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