Enterotoxigenic Escherichia coli - Escherichia coli: Pathotypes and Principles of Pathogenesis - page 179

Devasia et al., 2006 ) attests to the fact that even in industrialized countries these
organisms can cause serious harm. While some outbreaks can be traced to impor-
tation of food from beyond our borders ( MacDonald et al., 1985 ), in many cases
the ultimate source of ETEC is unclear ( Beatty et al., 2004 ). Because screening
for ETEC is not routinely performed in clinical microbiology laboratories, these
organisms usually escape recognition in sporadic cases and are only identified
during the course of investigation of large clusters of patients presenting with
diarrheal disease ( Jain et al., 2008 ). On systematic screening of patients with
diarrhea, domestically acquired ETEC infections have been identified in studies
from Sweden ( Svenungsson et al., 2000 ) and in Minnesota ( Beatty et al., 2004 ),
suggesting that these organisms are responsible for some small percentage of
sporadic diarrheal illness in industrialized countries including the US. One of
the larger recorded outbreaks occurred in the suburban Chicago area when a
single delicatessen catered multiple events, disseminating ETEC-laden food,
ultimately affecting thousands of people ( New Tork Times, 1998 ; Beatty et al.,
2004 ).
MOLECULAR PATHOGENESIS
Regulation
cAMP receptor protein (CRP) modulation of gene expression
in ETEC
Like other pathogens, ETEC respond to their environment by modulating
virulence gene expression, often as a result of sensing small molecules such
as glucose. Interestingly, some genes such as those encoding LT are opti-
mally expressed in the presence of glucose (catabolite activation), while other
genes such as those involved in elaboration of some pili, including CFA/I, are
repressed by glucose (catabolite repression). As in other important pathogens
( McDonough and Rodriguez, 2012 ), cyclic AMP appears to play a central role
in modulating the expression of these and other ETEC virulence molecules.
High levels of glucose inhibit bacterial adenylate cyclase and reduce levels of
cAMP and consequently its interaction with the cAMP receptor protein (CRP).
In the case of heat-labile toxin, the CRP-cAMP complex represses expres-
sion of the eltAB genes encoding LT; eltAB genes are therefore de-repressed or
stimulated in the presence of glucose as cAMP intracellular concentrations fall
and there is no CRP-cAMP complex to bind to the eltA promoter region and
inhibit initiation of transcription by RNA polymerase ( Bodero and Munson,
2009 ) ( Figure 6.1 ).
Recent studies in non-pathogenic strains of E. coli demonstrate that more
than 100 genes are modulated in response to CRP ( Zheng et al., 2004 ). Similarly,
ETEC have adapted this central regulatory mechanism to modulate expression
of a number of other virulence genes including tibA ( Espert et al., 2011 ) , and the
heat-stable toxin gene, estA ( Bodero and Munson, 2009 ) ( Table 6.1 ).