Capsule and lipopolysaccharide - Escherichia coli: Pathotypes and Principles of Pathogenesis - page 535

phosphorylated Kdo residue ( Horstman et al., 2004 ). It has been proposed that
ETEC is a milder disease than cholera, in part due to the fact that large amounts
of CT can reach host cells while LT is prevented from doing so because of its
association with the outer-membrane vesicles.
LPS and hemolytic uremic syndrome
Hemolytic uremic syndrome (HUS) is a disease characterized by hemolytic ane-
mia, acute kidney failure, and low platelet count (thrombocytopenia) and most
often occurs following an infection with Shiga-toxin-producing E. coli such as
strains belonging to serotype O157:H7. Activated platelets express P-selectin on
their cell surfaces which causes platelet aggregation and leukocyte binding due
to the fact that leukocytes constitutively express the P-selectin ligand, PSGL-1.
Normally, this allows leukocytes to migrate to areas of inflammation but patients
with HUS have increased levels of platelet-leukocyte aggregates in the blood
( Stahl et al., 2009 ). These microparticles also express tissue factor (TF), which
contributes to the prothrombotic state where the continued activation and subse-
quent aggregation of platelets leads to low platelet counts. In vitro, LPS is able
to induce platelet and leukocyte activation and to increase the amount of plate-
let-leukocyte aggregates in blood by causing cells to release proinflammatory
cytokines ( Guessous et al., 2005 ; Harrison et al., 2005 ; Stahl et al., 2009 ). Treat-
ment of human microvascular endothelial cells with O55-derived LPS causes
an increase in the secretion of the neutrophil-recruiting cytokine IL-8, followed
by secretion of leukocyte-activating cytokines, SDF-1α, and SDF-1β ( Guessous
et al., 2005 ). Macroarray and real-time PCR analysis of monocyte cell lines
has shown that O157 LPS causes an up-regulation of proinflammatory cyto-
kines, such as macrophage inflammatory protein 1α (MIP-1α), MIP-1β, TNF-α,
IL-1β, IL-8, and growth-related oncogene β (GRO-2) ( Harrison et al., 2005 ).
This is followed by secretion of monocyte chemoattractants MIP-1α and MIP-
1β, as well as the neutrophil chemoattractant GRO-2 ( Harrison et al., 2005 ).
LPS induces TF expression on monocytes and to a lesser degree on neutrophils,
likely a result of the increase in platelet-leukocyte aggregates, which leads to
an increase in the release of TF into the plasma ( Stahl et al., 2009 ). O157 is a
more potent inducer of platelet-leukocyte aggregation than other enterohemor-
rhagic E. coli- associated LPS antigens and has been detected using anti-O157
antibodies on platelets, monocytes, and neutrophils from several HUS patients
( Stahl et al., 2009 ). LPS-induced aggregation is enhanced by high shear forces,
such as those found in the renal cortex, which could contribute to the formation
of microthrobi in the kidneys ( Stahl et al., 2009 ).
Capsules, O antigen, and UPEC
The predominant cause of urinary tract infections (UTIs) is uropathogenic
E. coli (UPEC). Acquiring a UTI involves migration of the bacteria through the