Transcripts
DR. LINGWOOD:
Okay. Then, to summarize my
opinions as far as the risk factors for HUS,
which as far as I'm concerned all relate to
receptor binding -- so firstly is the Gb3
expression. If cells don't express Gb3, then they
are never sensitive to toxins.
I've already said fatty acid
chain length can modulate Gb3 binding. And I
didn't show you this, but the phospholipid
membrane environment can also affect Gb3 binding.
These plasma membrane lipid
domains can organization intracellular routing.
The Gb3 fatty acid chain lengths, affects VT
intracellular targeting. And Gb3 can be induced
by cytokines. And I mentioned a butyrate. I
showed you butyrate will induce the expression of
Gb3. Now, one thing I haven't pointed out, and
indeed haven't done research for yet but it's an
idea that I'm surprised nobody has looked at, is
butyrate is a metabolic intermediate in the
pathway in fatty acids metabolism of many
organisms.
So it could well be that if you
had an infection with some other organism which
is making a lot of butyrate at the time of VTEC
infection, then you would actually have a GI
system there that was generating a stimulator of
Gb3 synthesis during the infection. So that
would obviously greatly increase your
susceptibilities and that's a project that I'm
planning with Dr. Tarr that we should really
look and see what the concommittant infections
are and whether they produce short chain fatty
acids.
