Biology Reference
In-Depth Information
A
Shigella
9
Apical side
1
Enterocyte
M cell
6
Nucleus
8
5
7
Basolateral side
4
2
3
Polymorphonuclear
leukocyte
Macrophage
FIGURE 7.1 Stages in the invasion and intercellular spread of Shigella . Initially, bacteria trans-
cytose through microfold (M) cells of the intestinal epithelium (1), after which they are phagocy-
tosed by resident macrophages (2). The bacteria escape the macrophage phagosome and ultimately
induce pyroptosis and death of the host cell to gain access to the basolateral side (3). Bacteria are
then free to invade enterocytes via a T3SS-dependent process (4). Once inside the epithelial cell,
the bacteria lyse the single-membrane phagosome to avoid killing and replicate inside the host cell
cytosol (5). Bacteria polymerize host cell actin (6) creating an actin 'tail' that promotes cell-to-
cell spread (7). Once inside a second epithelial cell, Shigella escapes the new double-membrane
phagosome (8). Bacterial replication and spread continues throughout the colonic mucosa. Finally,
infected epithelial cells undergo necrosis and these dying cells release bacteria into the intestinal
lumen, where they may disseminate to the next host via the fecal-oral route (9). To maximize inva-
sion, Shigella -infected epithelial cells induce a massive influx of polymorphonuclear leukocytes
(PMNs) through the actions of chemoattractants IL-8 and hepoxilin A3 (HXA3). The transepithelial
migration of these PMNs disrupts the intestinal lining, allowing the bacteria to transverse between
the epithelial cells to ultimately reach the basolateral membrane for subsequent invasion (A). Figure
illustrated by Kym Bliven.
While it is necessary for Shigella to be able to multiply within the host epi-
thelial cell after invasion, intracellular multiplication is not sufficient to cause
disease. The bacterium must also be able to spread through the epithelial lining
of the colon by cell-to-cell spread in a manner that does not require the bacte-
rium to leave the intracellular environment and be re-exposed to the intestinal
lumen ( Figure 7.2 ). Mutants of Shigella that are competent for invasion and
multiplication but are unable to spread between cells in this fashion have been
isolated. These mutants established intracellular spread as the fourth hallmark
of Shigella virulence and will be discussed in a later section.
Along with the ability to colonize and cause disease, an intrinsic part of any
bacterium's pathogenicity is the regulatory circuitry for controlling expression
of virulence genes. Virulence in Shigella spp. and EIEC is regulated by tem-
perature. After growth at 37°C, virulent strains of Shigella are able to invade
mammalian cells but when cultivated at 30°C, they are non-invasive. This non-
invasive phenotype is reversible by shifting the growth temperature to 37°C
where the bacteria re-express their virulence factors ( Maurelli et al., 1984 ).
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