Biology Reference
In-Depth Information
attempts to correct the altered ion levels induced by these effectors by reducing
the intake of water, leading to increased water in the lumen, resulting in watery
diarrhea.
This combined decrease in the activity of SGLT1, DRA, and NHE3 impairs
the luminal NaCl absorption, leading to decreased water absorption potentially
through incorrectly localized AQPs, producing the pathophysiology of EPEC-
induced early diarrhea.
Altering junctional complexes
Intestinal epithelial cells are polarized so the apical side faces the lumen and
contains microvilli and the basal side interacts with the underlying lamina.
Junctional complexes (adherens junctions, densosomes, and tight junctions)
form on the apical side of the epithelial cells to connect adjacent cells (adherens
junctions and desmosomes) and to act as a regulatable barrier for passage of
ions and electrolytes, resulting in cell polarity (tight junctions). Tight junctions
are dynamic multi-protein complexes which contain occludin and members
of the claudin family, cytoplasmic scaffolding proteins, including the zonula
occludens family (ZO1, ZO2, and ZO3), and signaling molecules. EPEC can
dephosphorylate and remove occludin from TJs in a T3SS-dependent manner
(
Simonovic et al., 2000
) and in vivo EPEC was shown to redistribute occludin
in the ileum and colon (
Shifflett et al., 2005
). The T3SS effectors Map and EspF
are both able to effect occludin distribution in polarized Caco-2 monolayers
(
Dean and Kenny, 2004
) although the mechanisms are unknown.
EspI (NleA) also disrupts intestinal tight junctions potentially through its
ability to disrupt protein trafficking (
Thanabalasuriar et al., 2010
). EspI disrupts
protein trafficking by binding to a protein in the COPII coat, SEC24, inhibiting
COPII vesicle function (
Kim et al., 2007
). COPII vesicles mediate anterograde
trafficking of proteins from their sites of synthesis in the endoplasmic reticulum
to other membrane compartments in the cell and are a crucial first step in the
cell secretion pathway. COPII cargo includes membrane and luminal proteins
and Sec24 has an important role in sorting and selecting cargo for inclusion in
COPII vesicles. It is therefore proposed that EspI disruption of COPII vesicles
hampers the replenishment of TJ proteins, causing a sequential loss of func-
tional TJ complexes (
Thanabalasuriar et al., 2010
).
A number of tight junction proteins including claudin-1, ZO-1, ZO-2, and
occludin are altered by the presence of
Shigella
; however whether a T3SS effec-
tor is responsible for these changes is unknown (Sakaguchi et al., 2002).
CONCLUSION
EPEC/EHEC and
Shigella
have thus developed a diverse and sophisticated
array of T3SS effectors to reprogram the host for the advantage of the pathogen.
While some effectors are multifunctional, others appear to have overlapping
Search WWH ::
Custom Search