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Shigella dysenteriae ( Trofa et al., 1999 ). Shiga toxin-producing E. coli (STEC)
have also been described and are associated with a range of symptoms in the
human host, from mild diarrhea to severe hemorrhagic colitis (see Chapter 5)
( Kaper et al., 2004 ). Most importantly, STEC are associated with hemolytic
uremic syndrome (HUS) ( Corrigan et al., 2001 ), which differentially affects
young children in developing countries. The E. coli outbreak in Europe in the
summer of 2011 was caused by an isolate that had the Shiga-toxin phage in the
context of a phylogenetic group that did not previously harbor this genetic ele-
ment ( Frank et al., 2011 ; Rasko et al., 2011 ). If strict molecular definitions are
observed, the outbreak isolate could be classified as an STEC, but not EHEC,
as the majority of the genome was most similar to an enteroaggregative E. coli
(see below). These findings from genomic studies highlight the limitations with
regard to inferred phylogeny of the current typing schema that rely on mobile
genomic regions as biomarkers or small amounts of DNA for typing.
The STEC isolates can be segregated into groups that either contain the Locus
of Enterocyte Effacement (LEE) ( McDaniel et al., 1995 ) pathogenicity island
( Kaper et al., 2004 ) and those that do not. The LEE encodes a type III secretion
system that injects infectors into the host cell that results in the formation of
attaching and effacing lesions (see Chapters 5, 6, 14, and 15) ( Donnenberg and
Kaper, 1992 ; McDaniel et al., 1995 ). LEE-positive STEC are frequently termed
enterohemorrhagic E. coli (EHEC), due to the frequent manifestation of hemor-
rhagic colitis in infected hosts. LEE-positive isolates can also be classified as
a ttaching and e ffacing E. coli (AEEC), which also includes enteropathogenic
E. coli (EPEC, see below). Thus there is some ambiguity in how these isolates
that can be phylogenetically related ( Figure 2.1 ) are classified based on the
presence or absence of specific molecular markers. As with the other pathovars,
it is hoped that continued sequencing will identify stable regions of the genome
that can be utilized as potential biomarkers for rapid and accurate classification
of these pathogens. It is possible that in some cases, as with the EHEC/STEC
division, that multiple markers will be required.
The first EHEC genome sequenced was O157:H7 strain EDL933, which
was isolated from an outbreak in Michigan ( Perna et al., 2001 ). A compari-
son of this genome with K12 identified ∼1400 new genes associated with
virulence factors, prophages, and genes associated with variable novel meta-
bolic pathways. This publication was followed closely by a manuscript that
described the sequence of O157:H7 strain Sakai ( Hayashi et al., 2001 ), which
was isolated from an outbreak in Japan ( Watanabe et al., 1996 ). The results
of this comparison identified 1632 proteins present in the Sakai strain and
absent in K12. These two isolates from the same pathovar provided the data
for the first intrapathotype comparisons ( Kudva et al., 2002 ). These studies
provided evidence of greater intrapathotype diversity than was previously rec-
ognized and signaled that the evolutionary processes leading to the creation
of these pathogens were not likely to be simple, linear or easily understood
(see Chapter 3).
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