00:01
So the shigella come in four species, shigella
dysenteriae, shigella flexneri, shigella
boydii and shigella sonnei, and these are
all capable of causing dysentery.
00:16
These bacteria are spread from person-to-person
via contact or by
contaminated food or water, and you don't
need a lot of these bacteria to cause an
infection, only a hundred or a thousand are
enough, so very minimal contamination
of food for example or transmission of
minimal numbers is enough to initiate an
infection. So you ingest these organisms,
they go to your intestine and they
invade through M cells. Now M cells you
may remember from an earlier lecture
about bacteria are the cells that are
interspersed throughout the other
epithelial cells and these cells are
constantly sampling the lumen of the
intestine to make sure there aren't
any dangerous antigens there. So they take up
things very actively and pass them
through to immune cells on the lower
side of the intestinal wall. Many
pathogens take advantage of M cells
to enter the host and shigella is one
of them. They bind to M cells and they
get passage through the M cell and then
they're released onto the underlying
space which is called the lamina propria.
In this process, M cells are often
full of macrophages that are there, sampling
antigens, they take up the shigella
in this case, but the shigella are not
destroyed by the macrophages. They escaped the
phagosome in the macrophage which is
taking them up,
get outside and they can spread elsewhere,
but this transitory experience
with the macrophage causes the release of
cytokines from the macrophage, that
causes inflammation of course. The cytokines
recruit other cells to the
infected area and all of this causes the symptom
of infection. These shigella, by
the way, which are shown as the red oblong
bacteria here, can then invade epithelial
cells from the bottom. So they've come
in through the
M cell, they're in the lamina propria and
now they go back into the epithelial
cell from the bottom. They ride the host cytoskeleton
up to the surface again and
now they're back on the surface of the
epithelial cells. And they can go through
multiple cycles of reinfection and being
brought to the top again, eventually this
destroys M cells as well as epithelial cells.
The cells come off, so you end up
having erosion of the gut wall or an ulcer,
so this is a physical removal of
cells as a consequence of bacterial inflammation.
You have an ulcer and
in the process of doing this, many other
immune cells have been trying to clear
the infection, including neutrophils, major
defense cells for many bacterial
infections as we've mentioned before. These
cells die in the process and they
accumulate in the stool and that's what
provides the pus for the stool, the
presence of all these dead immune cells. So
the lesion in the wall, the dying
neutrophils, that gives you the blood and
the pus in the stool, part of the dysentery.
03:22
One of the species of shigella
produces another toxin called shiga
toxin and this toxin has a specific effect
in our cells. It cleaves the large
ribosomal subunit, the 60S subunit and that
stops protein synthesis, so that
basically kills the cells and is partly
responsible for the cells leaving their
position in the epithelium and causing that
ulcer. You do need to take oral
fluids to take care of a shigella induced
dysentery, you don't need
intravenous fluid, you can just take this
by mouth.
03:58
You can use antibiotics, but there's a lot of
resistance out there
and they are not effective.