Transcripts
DR. LINGWOOD:
Now we call the E. coli toxins
verotoxins, but they're also called Shiga toxins,
and this is the pathogenic molecule that the
0157:H7 makes and it is responsible for all the
clinical pathology, at least initially, that can
develop into HUS.
So as I've already said, this
is associated with Hemolytic Uremic Syndrome and
the precursor, Hemorrhagic Colitis in the
gastrointestinal tract. It's a family of toxins,
it's not just one toxin. Primarily, it's VT1 or
Shiga toxin 1. But VT2 is also significant.
VT2c is rarely seen, and then there's a related
VT2e, which causes disease in pigs, not in
humans, but it's structurally very similar to VT1
and VT2.
There are subunit toxins, which
means they compose two parts, an "A" subunit,
which is the enzymatic activity, that means it
is the cytotoxic component.
It cleaves to what's known as
an adenine base from RNA in the ribosome. The
ribosome is what carries out protein synthesis.
So by doing that, it prevents protein synthesis.
When you prevent protein synthesis, you kill the
cell.
The receptor binding "B" subunit
is smaller, very small, only five kilodaltons and
it's a pentameter, so it's a five membered ring,
like a doughnut. And the "A" subunit, which is
a single structure, fits in like this.
And the "B" subunit is what
binds to the receptor on the sensitive cells.
And that's really what I'm going to be talking
about.
My opinion is that the risk
factors in terms of HUS are all related to the
how the toxin targets different cells and the
subsequent pathological effects. And that relies
on the ability of the "B" subunit to bind its
receptor.
And the receptor is a
glycolipid, which I'm going to be referring to
as Gb3, I will show you the structure in a
minute, and that is expressed on the surface of
sensitive cells.
