00:01
Let’s talk a bit about bacterial toxins.
These are molecules produced by various bacteria
that alter the normal metabolism of host cells,
and they are often responsible for the major
symptoms of bacterial infection. And there
are many different kinds of toxins that are
produced, which we will talk about briefly.
Interestingly, this is in direct contrast
to viral infections, in which very few viral
toxins have been identified; they cause disease
in very different ways from bacteria. Now
we recognize different classes of bacterial
toxins, some are called exotoxins, because
they are secreted by the bacterium into the
extracellular environment. These exotoxins shown
on this picture have a typical AB structure,
they have subunits, separate subunits consisting
of an A component and a B component. Typically
the way they work, is they are secreted by
the bacterium and they bind a receptor, shown
here in R, on the surface of the eukaryotic
cell, on the surface of our cells. They are
then taken up into the cell by the endocytic
pathway, and typically the A component, which
is the active component, is released from
the receptor binding component, makes its
way into the cytoplasm where then has its
effect on cells. There is another class of
toxins called the type III cytotoxins, they
are shown on the right of the diagram, where
we see an outline of a rod shaped bacterium and
what looks like a syringe, injecting molecules
into the host cell. Those are type III cytotoxins,
they are directly injected into the host cell
by a structure on the bacterium called a secretory
injection system and these have evolved just
to inject toxins into the cell. These secretory
systems act by introducing molecules into
cells to alter their behavior. Other toxins
are produced by bacteria, that act at the
surface of host cells, some of them bind to
pattern recognition receptors and induce the
production of cytokines, which have lethal
effects, there are also pore forming toxins which
make holes in cell membranes and make them
die. And finally there are toxins called superantigens
that bind to T cell receptors and major histocompatibility
receptors, and induce the synthesis of many,
many toxic cytokines. And finally there are
proteins called exoenzymes produced by bacteria
that modulate targets in the extracellular
matrix.
02:49
Let’s look at toxins in a bit more detail.
I mentioned that they typically have an AB
structure. The diphtheria toxin consists of
one molecule of the A and one molecule of
the B, again the B is the receptor binding
component, the A is the effector portion that
actually has an effect on the host cell. Diphtheria
toxin, the A portion blocks cell protein synthesis,
the A portion ADP ribosylates, an elongation
factor for translation eEF-2, it stops host
cell protein synthesis and kills the cell.
Cholera toxin is composed of a single A subunit
and 5 B subunits. This toxin elevates intracellular
cyclic adenosine monophosphate in the epithelium
of the small intestine and that causes movement
of fluid into the lumen and a classic diarrhea
associated with cholera. And finally the Anthrax
toxin, the highly lethal anthrax toxin is
composed of two A and a B subunits, and again
the B subunit binds the cell receptor.
03:57
Two toxins that are well known, botulinum
toxin, produced by C. botulinum and tetanus
toxin produced, by C. tetani clostridium,
are neurotoxins. These toxins elaborated by
their bacteria at different sites make their
way through the circulatory system and the
lymph system. Tetanus toxin for example,
causes muscles to contract uncontrollably,
and they cause what we call spastic paralysis.
04:25
On the other hand, botulinum toxin blocks
muscle contractions, so the muscles get flaccid,
this is called flaccid paralysis, so two very
different effects on the central nervous system.
04:41
The type III cytotoxins we mentioned briefly
before, they're shown on the right-hand part
of this screen, they are injected by the bacterium
into the host cell by a type III secretion
apparatus. Bacteria have a number of different
kinds of secretion apparati which are used
to inject effector molecules into the host
cell to get them to do what they want, and
these have their own ways of altering the
biochemistry of the cell to cause pathology.
05:10
Type III cytotoxins are found in a wide range
of bacteria, for example Salmonella, Shigella,
Pseudomonas, Cholera and the Plague bacilli,
all produce type III toxins of various sorts
and we will mention a few of these and how
they work in a few moments.