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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no longer active.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.
