Type 3 secretion effectors - Escherichia coli: Pathotypes and Principles of Pathogenesis - page 470

Changing the absorptive surface area of the gut, modulating the junctional
complexes, or altering selective channels/porins all effect the integrity of the
intestinal epithelial layer. However, in addition the gut epithelium undergoes
continuous self-renewal to maintain tissue homeostasis and eliminate damaged
cells and changes in apoptosis will alter the turnover of gut epithelium and con-
tribute to the disruption of gut integrity. Host inflammatory responses, such
as migration of polymorphonuclear cells towards the gut lumen, also strongly
disrupt the integrity of the epithelium layer and are thought to be the major con-
tributors to Shigella- and EHEC-mediated diarrhea.
Microvilli effacement
Below the epithelial monolayer lies the lamina propria and submucosa. The
undulating ridges of the intestinal submucosa, the folds of the lamina propria
forming the villi and crypts, and the finger-like microvilli on epithelial cells
maximize the absorptive surface of the small intestine. The effacement of the
microvilli, a defining feature of the A/E lesion results in a reduced surface area
for normal absorptive processes. Effectors involved in cytoskeleton remodel-
ing and adherent junction manipulation contribute generally to the effacement
of the microvilli, however specific interactions targeting microvilli effacement
are less well understood. A single microvillus contains a core F-actin bundle
which is internally stabilized by villin and fimbrin and laterally stabilized by
myosin 1a:calmodulin bridges to the plasma membrane. The microvillus actin
core is tethered into the cellular actin filament at the terminal web, which con-
tains amongst other proteins, myosin 2, spectrin, tropomyosin, and α-actinin
( Figure 15.4 A).
Effacement has been described as a two-step process, requiring the coopera-
tive action of three injected effectors (Map, EspF, and Tir) as well as intimin. It
has been suggested that Tir and intimin predominate in the first step of efface-
ment where bacteria sink into the brush border, while EspF and Map predomi-
nate in the ensuing microvillus destruction ( Dean et al., 2006 ). Interestingly
F-actin is not seen in the detached microvillar material but is thought to be
contracted into the cell ( Dean et al., 2006 ). As previously explained EspB can
interact with the myosin superfamily, specifically with the C-terminal region of
the motor domain of myosins, which normally interacts with actin filaments,
competitively inhibiting the myosin:actin interaction ( Iizumi et al., 2007 ). Myo-
sins 1a and 2 ( Figure 15.4 A), as well as 1c, 5, and 6 localize to and stabilize the
microvilli of enterocytes, and the interaction of EspB with myosins therefore
directly contributes to the effacement of the microvilli.
Altering ion exchange and water transport
Increased secretion or decreased absorption of Cl - increases the luminal
Cl - concentration and leads to increased water in the lumen. EPEC reduces