Biology Reference
In-Depth Information
in bench-top next generation sequencing platforms have provided independent
investigators with the ability to sequence isolates of E. coli . As of September
2012, there are >1000 registered E. coli sequencing projects available in Genbank
( http://www.ncbi.nlm.nih.gov/ ). These sequencing projects may further clarify the
evolutionary history of the species, the diversity of gene content within the spe-
cies, and identify genes associated with pathogenesis within each pathovar. Ide-
ally, the ongoing genomic and phylogenomic studies will identify regions of the
genome that are not encoded on mobile elements, and thus may represent more
stable and effective biomarkers for each pathovar. Additionally, the sequencing
will provide deeper insight into genomic diversity, combined with studies of the
transcriptome, will provide clues into the regulatory networks of these pathogens.
This chapter will be separated into descriptions of the genomic studies that
have been completed on isolates on each of the specific pathovars.
UROPATHOGENIC E. COLI
Uropathogenic E. coli (UPEC) are thought to be innocuous in the gastrointesti-
nal tract, but become pathogenic in the urinary tract ( Chen et al., 2006 ; Schwartz
et al., 2011 ). High-throughput sequencing has shed light on the diverse genomic
organization and distribution of virulence factors in this pathotype. The UPEC
are the prototypes of the extraintestinal pathogenic E. coli (ExPEC) isolates
and often people refer to UPEC isolates as ExPEC isolates, but in this case
we will only discuss the UPEC, as the majority of the sequencing has focused
specifically on the UPEC.
The first UPEC isolate, CFT073, was sequenced, as a collaborative effort,
by Welch et al., in 2002. CFT073 was isolated from the blood of a patient with
pyelonephritis; the genome consists of 5.2 Mbp, 5533 protein-coding genes, and
no identified virulence plasmids. This strain is considered to be the prototype
UPEC isolate, but the isolation from the blood of a patient suggests that it may
be particularly pathogenic in comparison to other UPEC isolates. UPEC have
acquired virulence genes that allow them to survive, and possibly thrive, in the
GI tract but result in a disease presentation in the urinary tract. These genes
are often found on horizontally acquired pathogenicity islands ( Hacker et al.,
1992 ; Hacker and Kaper, 2000 ). The CFT073 sequence confirmed the presence
of previously described pathogenicity associated islands (PAIs) located at tRNA
genes pheV , pheU , and asnT . PAI- pheV contains genes for p ili a ssociated with
p yelonephritis ( pap ), aerobactin synthesis, hemolysin ( hly ), capsule synthesis,
and two autotransporters. PAI- pheU also contains pap genes as well as a sider-
phore receptor ( Welch et al., 2002 ). PAI- asnT is similar to the high pathogenicity
island of Yersinia pestis and contains yersiniabactin genes ( Perry and Fetherston,
2011 ). The location and composition of the PAIs in CFT073 were surprisingly
different from the known PAIs in two other well-studied UPEC isolates 536 and
J96 ( Swenson et al., 1996 ; Middendorf et al., 2001 ). The PAI- pheV of J96 also
contains hly but additionally encodes h eat r esistance h emmagglutanin ( hra ) and
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