Reservoirs of Extraintestinal

Pathogenic Escherichia coli

AMEE R. MANGES1 and JAMES R. JOHNSON2,3
1

School of Population and Public Health, University of British Columbia, Vancouver, BC V6T 1Z3, Canada;
2
Infectious Diseases Section, Veterans Affairs Medical Center, Minneapolis, MN 55417;
3
Department of Medicine, University of Minnesota, Minneapolis, MN 55455

ABSTRACT Several potential reservoirs for the Escherichia

coli strains that cause most human extraintestinal infections
(extraintestinal pathogenic E. coli; ExPEC) have been identied,
including the human intestinal tract and various non-human
reservoirs, such as companion animals, food animals, retail meat
products, sewage, and other environmental sources.
Understanding ExPEC reservoirs, chains of transmission,
transmission dynamics, and epidemiologic associations will
assist greatly in nding ways to reduce the ExPEC-associated
disease burden. The need to clarify the ecological behavior of
ExPEC is all the more urgent because environmental reservoirs
may contribute to acquisition of antimicrobial resistance
determinants and selection for and amplication of resistant
ExPEC. In this chapter, we review the evidence for dierent
ExPEC reservoirs, with particular attention to food and food
animals, and discuss the public health implications of these
reservoirs for ExPEC dissemination and transmission.

INTRODUCTION
The existence of important infection-causing ExPEC lineages (i.e., genetically closely related E. coli clones or
clonal groups) has been recognized for the past 40 years.
However, identication and detailed characterization
of specic lineages has only recently been advanced,
owing to the development of new methods for bacterial genotyping. Since ExPEC can colonize and persist
in the human intestinal tract without detriment to the
host, the operational denition of ExPEC is critical for
dening the chain of ExPEC transmission from nonhuman reservoir to human intestinal colonization to
active infection.
ExPEC clonal groups have been dened differently
over time largely in relation to the available phenotyping and genotyping technologies. Early studies

identied 10 to 15 O-antigenbased serogroups (of the

approximately 180 that occur in E. coli) as being associated with human extraintestinal infections (1, 2). The
addition of K and H antigen typing provided ner resolution. DNA-based genotyping methods, such as multilocus sequence typing (MLST) have further advanced
our understanding of these lineages. For the purposes
of this review, ExPEC is dened as isolates (i) recovered
from extraintestinal infections, (ii) possessing known
ExPEC virulence factors, (iii) exhibiting MLST sequence
types associated with extraintestinal infections, and/
or (iv) exhibiting classic ExPEC-associated serogroups/
serotypes in conjunction with typical ExPEC virulence
factor proles or phylogenetic group membership (e.g.,
groups B2 and D).
Certain major E. coli lineages have been implicated repeatedly in epidemiologic studies as the cause of a large
proportion of human extraintestinal E. coli infections
(Fig. 1). Many such groups are multidrug-resistant and
likely contribute signicantly to the ongoing populationlevel increase in antimicrobial-resistant human E. coli
infections. Here, for consistency, we identify specic
ExPEC lineages by O:K:H serotype (if known), phyloReceived: 26 July 2012, Accepted: 9 October 2014,
Published: 4 September 2015
Editors: Matthew A. Mulvey, University of Utah, Salt Lake City, UT;
Ann E. Stapleton, University of Washington, Seattle, WA; and
David J. Klumpp, Northwestern University, Chicago, IL
Citation: Manges AR, Johnson JR. 2015. Reservoirs of extraintestinal
pathogenic Escherichia coli. Microbiol Spectrum 3(5):UTI-00062012. doi:10.1128/microbiolspec.UTI-0006-2012.
Correspondence: Amee R. Manges, amee.manges@ubc.ca
2015 American Society for Microbiology. All rights reserved.

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Manges and Johnson

FIGURE 1 The tree, which is drawn to scale, was inferred

using the Neighbor-Joining method, based on concatenated
DNA sequences from the seven MLST loci. E. fergusonii was
used to root the tree, but for simplicity has been excluded. All
positions containing gaps and missing data were eliminated.
There were a total of 3423 positions in the nal dataset.
doi:10.1128/microbiolspec.UTI-0006-2012.f1

genetic group of origin (A, B1, B2, or D), and sequence

type (ST), as determined by MLST; for example,
O25:H4-B2-ST131. Several important ExPEC lineages
are highlighted based on their large contribution to
overall disease burden, including: O25b:H4-B2-ST131,
O25a:H4(a)-D-ST648, O11/O17/O77:K52:H18-D-ST69,
O15:K52:H1-D-ST393, (serotype: various)-D-ST117,
O1/O2/O18:K1:H7-B2-ST95, O6:K2:H1-B2-ST73, (serotype: various)-A-ST10, (serotype: various)-D-ST405,
and O75:K+:H5-B2-ST14. Since many of these groups
have been identied in surveillance studies focused on
extended spectrum -lactamase (ESBL)-producing E. coli,
ESBL-producing lineages tend to be overrepresented.

IMPORTANT ExPEC LINEAGES

E. coli O25:H4-B2-ST131, reported rst in 2008, is an
important new globally emerging pathogen (3, 4). This
clonal group is of major public health concern because
of its typically extensive antimicrobial resistance prole,
which often includes ESBL production, specically of
CTX-M-15, plus uoroquinolone resistance, and its
widespread distribution. E. coli O25:H4-B2-ST131 has
been identied primarily from human infections and

has been associated with travel, which may explain its

international spread over the past decade. In surveys
of human E. coli infections this group accounts for
a large fraction of cases overall (5), and up to 88% of
antimicrobial-resistant infections, depending on the
specic resistance phenotype (6).
E. coli O11/O17/O77:K52:H18-D-ST69 (also termed
CgA, for clonal group A) was identied initially in
an apparent outbreak of extraintestinal infections in
Berkeley, California, during which it accounted for 11%
of all urinary tract infections (UTIs) and 52% of antimicrobial-resistant UTIs (7). It has since been identied
around the world (8). This group often exhibits multidrug resistance and has been responsible for urinary
tract and more severe human extraintestinal infections
(811). Several studies found this group to cause approximately 10% to 20% of all human E. coli infections (8, 12,
13). A recent global survey suggested that the O11/O17/
O77:K52:H18-D-ST69 group is concentrated in North
America and may have emerged in the 1990s (13).
E. coli O15:K52:H1-D-ST393 was rst recognized
during an outbreak of extraintestinal infections from
1986 to 1987 in London, UK (14), and has subsequently
been identied across Europe (15, 16) and globally
(17). In the initial epidemic, O15:K52:H1 caused 26%
of all extraintestinal infections during a 1-year interval
(5, 14). This group also is typically multidrug-resistant
and has caused community-acquired extraintestinal
infections of all types (14, 16, 18, 19). It is closely
related to O11/O17/O77:K52:H18-D-ST69; both possess similar antimicrobial resistance and virulence factor
patterns and appear to share a common ancestor (20).
E. coli O6:H1-B2-ST73 was recently reported as a
leading cause (17% overall) of human extraintestinal
infections in the UK (21). This clonal group, like many
others, is associated occasionally with ESBL production (2123). It may represent a long-standing, humanadapted ExPEC group, since it has caused UTIs in
women in many geographic areas and over many years
(24).
E. coli (serotype: various)-D-ST405 is another globally disseminated, extensively antimicrobial-resistant
group (3, 2527). ST405 may be the next most important contributor after ST131 to the global dissemination of CTX-M-15 (3). Furthermore, an ST405 E. coli
isolate was recently encountered that produced multiple
ESBLs, including QepA1, CTX-M-15, and RmtB (28).
ST405 also has been associated with New Delhi metallo
(NDM) -lactamases (29). ST405 has been associated
with person-to-person transmission (26), but evidence
for non-human reservoirs is still lacking (24).

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Reservoirs of Extraintestinal Pathogenic Escherichia coli

E. coli (serotype: various)-A-ST10 or E. coli ST10

clonal complex (i.e., ST10 and closely related STs),
although typically encountered as an antimicrobialsusceptible, low-virulence human intestinal colonizer,
also has been associated with human infections and
ESBL production. This clonal group, members of
which have caused hospital and community-acquired
infections, was found to account for 7% of all human
clinical E. coli isolates in Calgary, Alberta, Canada (30).

OTHER NOTABLE ExPEC CLONAL GROUPS

E. coli O1/O2/O18:K1:H7-B2-ST95 is both a recognized avian pathogenic Escherichia coli (APEC) clonal
group (31) and a prominent human urinary tract and
meningitis pathogen, accounting for 6% of human extraintestinal clinical isolates in one study (21). E. coli
(serotype: various)-D-ST117 is another recognized
APEC lineage that has also been identied as a cause
of human UTI (32, 33). E. coli O75:K+:H5-B2-ST14, in
the past an important ampicillin-resistant clonal group,
has recently been associated with uoroquinolone resistance in Australia (34). E. coli (serotype: various)-DST648 has been associated with human disease in China
(35), Canada, and the Netherlands (36), and with NDM
-lactamases (37). Additionally, E. coli ST167, ST410,
and ST38 have also been identied in epidemiologic
studies of human extraintestinal infections; however,
less information is available concerning the dissemination and reservoirs for these E. coli clonal groups (23,
36, 3841). Given the wide distribution of several of
these E. coli clonal groups, efforts to identify their
reservoirs are needed.

THE HUMAN RESERVOIR OF ExPEC

An appropriate starting point for reviewing the sources
of human ExPEC is the human intestinal tract. The
human intestinal tract has long been recognized as a
reservoir of E. coli (42). ExPEC also are members of
the intestinal microbiota in a large fraction of healthy
individuals (42). However, in contrast to non-ExPEC
intestinal colonizers, once ExPEC gain access to other
body sites they can persist and cause disease. ExPEC
that cause UTIs typically follow a fecal-to-perineal/
vaginal-to-urethral transmission pathway within the
individual host (43, 44). ExPEC also sometimes cause
sepsis by entering the bloodstream directly, via translocation across the intestinal barrier (45). Importantly,
the intestinal microbiota also can serve as a reservoir of
antimicrobial resistance determinants for ExPEC (46,

47). Exposure to an antimicrobial agent can temporarily

increase the prevalence of antimicrobial-resistant E. coli
in the intestine, although this increase may be short-lived
for most antimicrobials (48).
Several studies have documented direct person-toperson transmission of ExPEC strains between household members and sexual contacts, in many instances
with linkage to subsequent extraintestinal infections
(4953). The exchange of ExPEC between sexual partners in particular could be one explanation for the
phenomenon of recurrent UTIs in some women, since
the male partner (who is not treated) may remain a
reservoir for re-infection of the woman. Although
strain sharing among household and sexual contacts
could increase the risk of future infection in a given
individual, spread of ExPEC or antimicrobial-resistant
E. coli from non-human or food reservoirs through
the entire population represents a larger public health
threat. Understanding how these organisms reach
the human intestinal tract could lead to strategies to
minimize transmission, thereby reducing the pool of
antimicrobial-resistant and pathogenic E. coli in the gut
available to cause disease.

ENVIRONMENTAL RESERVOIRS OF ExPEC

Surface water, rainwater, wild animals, sewage, and
wastewater efuents have all been investigated as possible environmental sources of ExPEC. Sewage may
contribute signicantly to the environmental dissemination or circulation of ExPEC due to the presence
of highly concentrated human fecal waste containing
ExPEC. To study environmental reservoirs is challenging because these sources tend to contain E. coli from
multiple sources (e.g., sewage may contain human, animal, and industrial waste). Microbial source tracking
is complicated by the difculty of assigning the E. coli
recovered in any given environment to a particular
source. Furthermore, the methods used to discriminate
and describe ExPEC and other types of E. coli can be
highly variable. In this section, water and other potential
environmental sources of ExPEC are reviewed.
Survival of ExPEC during sewage treatment, leading to possible environmental contamination, has
been investigated in several studies, which identied
ExPEC-associated phylogenetic groups, virulence genes,
and lineages among E. coli from sewage samples. For
example, in a study of four sewage treatment plants
60% of E. coli sewage isolates belonged to ExPEC
phylogenetic groups B2 and D and a large fraction
possessed hlyA (74%) and iroN (82%), while smaller

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proportions possessed P mbrial genes papAH, papEF,

papC, and the cytotoxic necrotizing factor 1 (cnf1) gene
(54). Another study found a high prevalence of group D
E. coli (37%) and quinolone resistance (56%) among
E. coli sewage isolates (55). Both studies identied putative ExPEC isolates in the nal efuent, suggesting that
treated water released into the environment may contain
viable ExPEC (54, 55).
Notably, two important ExPEC lineages were identied in sewage sources, including E. coli O25:H4-B2ST131 (treated wastewater and river water) (56, 57)
and E. coli O11/O17/O77:K52:H18-D-ST69 (sewage
efuent) (58). It is clear that, despite sewage treatment,
ExPEC persist throughout the treatment process, with
their presence risking contamination of surface water
(54). Investigation of the movement of ExPEC in treated
sewage and other wastewater sources is needed, since
these sources may participate in the environmental cycling of ExPEC clonal groups that cause disease in
humans and animals.
Surveillance studies have consistently identied
antimicrobial-resistant and pathogenic E. coli in natural bodies of water and recreational waterways (59
61). In one study, 40% of E. coli isolates from coastal
marine sediments represented phylogenetic groups B2
and D, and most of these contained at least 1 of 11
ExPEC virulence genes (61). Hamelin et al. used a DNA
microarray containing probes to 348 antimicrobial resistance genes and virulence genes from all E. coli
pathotypes to characterize E. coli from recreational and
river waterways. Isolates were dened as uropathogenic if positive for at least one of the following: pap
genes, hlyA, S mbriae-encoding genes, chuA, fepC,
cnf1, irp1, irp2, fyuA, iroN, or usp (60, 62). From Lake
Ontario recreational water, 73% of E. coli isolates
were uropathogenic, with most belonging to phylotypes
B2 and D, whereas from six different river, estuary,
and offshore lake locations, 26% of E. coli were uropathogenic (60, 62). Similarly, Mhldorfer et al. found
that 41% of E. coli isolates from surface water samples
from the Elbe River in Germany contained ExPECassociated genes (63). Finally, rainwater contamination
with ExPEC, as dened based on ExPEC virulence
genes, was documented for 68% of rain barrels in
Australia, which was concerning since many of the
barrels were used as a potable water source (64).
Wild animals, particularly wild birds, also have
been investigated as an environmental source of
antimicrobial-resistant and pathogenic E. coli (6569).
A study of ESBL-positive E. coli from yellow-legged
gulls in France identied CTX-M-1-positive E. coli

representing the ST23 complex and the ST533 clonal

group, which previous studies associated with UTIs
(65, 7073). Additionally, E. coli ST648 was identied in wild birds in Germany (74). A review of ESBLproducing E. coli recovered from wildlife sources
documented the diversity of E. coli colonizing different
animal hosts, but highlighted the occurrence primarily
in wild birds of ExPEC-associated STs, including
ST69, ST131, ST405, ST10, and ST648 (75).
Thus, compelling evidence exists that ExPEC occurs
in sewage and other environmental sources, including
wild animals and water. However, to date such ExPEC
have not been tested in established animal models of
human extraintestinal disease for their potential human
extraintestinal pathogenicity. This step would provide
important conrmation that wild animals, sewage,
and water could act as reservoirs for ExPEC capable
of causing infections in humans.

COMPANION ANIMAL
RESERVOIRS OF ExPEC
Companion animals, which develop similar types of
extraintestinal infections as their human guardians, have
also been identied as a reservoir of human ExPEC (76
78). Surveys of the E. coli causing infections in pets, and
surveillance studies at veterinary hospitals, have documented the circulation of genetically related and frequently antimicrobial-resistant ExPEC in dogs, cats, and
other animals that live in close contact with humans (79,
80).
Intestinal colonization by ExPEC has been demonstrated in companion animals. A study of E. coli from
canine fecal samples identied approximately 50% of
isolates as ExPEC by virulence factor genotyping and
direct comparison with reference human ExPEC isolates (81). Environmental contamination with feces, and
consequent transmission of fecal-source E. coli between
dogs, in particular, likely occurs frequently. Multidrugresistant E. coli isolates from rectal swabs from a population of dogs were similar (according to phylogenetic
group and pulsed eld gel electrophoresis [PFGE]) to
the E. coli causing extraintestinal infections in animals
(82). The ExPEC isolates were closely related, persistent,
and present in multiple species, including cats, dogs, and
horses (82).
Closely related or indistinguishable ExPEC strains
have been recovered from humans and their companion
animals, suggesting transmission in either direction.
For example, in one study, an E. coli strain (O1:K1:H7B2-ST95) was shared extensively (present in 45% of

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Reservoirs of Extraintestinal Pathogenic Escherichia coli

samples) among household members and the family dog,

and caused a UTI in the mother (83). Similarly, an E. coli
O6:K2:H1-B2-ST73 strain was shared between family
members and the family dog, which developed UTI
due to this strain (51, 84). The human ExPEC lineages
O6:K15:H31-B2-ST127 and O4:K54:H5-B2-ST493 also
have been identied in dogs, cats, and humans (85).
These results were conrmed using a set of E. coli recovered from dogs alone, where the canine isolates exhibited
ExPEC virulence factors related to those of human reference ExPEC isolates (85, 86). Additionally, E. coli O75:
K+:H5-B2-ST14 was recently identied in pet dogs (34).
ESBL-producing E. coli, some from ExPEC-associated
clonal groups, also have been recovered from companion
animals in diverse locales. ESBL (specically, CTX-M)positive E. coli recovered from stray dogs in Korea included members of the ST10, ST38, ST93, and ST95
clonal groups, whereas CMY-2-positive E. coli included
ST405 and ST648 (87). CTX-M-positive E. coli ST648
was recovered from companion animals in Japan (88).
Closely related ESBL (CTX-M-15)-positive E. coli O25:
H4-B2-ST131 isolates were identied in humans, companion animals (primarily dogs), and other animals from
several European countries (89). Likewise, in Australia,
42% of uoroquinolone-resistant human ExPEC isolates
belonged to three ExPEC lineages (O25:H4-B2-ST131,
O11/O17/O77:K52:H18-D-ST69 and O15:K52:H1-DST393), representatives of which also were identied
among contemporaneous clinical isolates from companion animals (80). These ndings demonstrate that the
extensive clonal spread of E. coli O25:H4-B2-ST131 is
not limited to humans. Another study provided strong
evidence for direct transmission of an E. coli O25:H4B2-ST131 strain among multiple companion animals
within a single household (52). This strains PFGE prole
closely resembled the PFGE proles of E. coli O25:H4B2-ST131 isolates from human infections from other
studies, implying cross-species transmission at some
point (90). Additional ExPEC strains were also shared
between dogs and cats in this study, again suggesting
cross-species transmission within a household (51).
These results support the hypothesis that ExPEC
from companion animals and humans represent overlapping populations, with certain ExPEC lineages capable of causing infections in and/or colonizing either
host group. Related to this, antimicrobial resistance
among ExPEC may be further selected by antimicrobial
therapy given to companion animals, leading to additional exposure of humans to antimicrobial-resistant
ExPEC through routine contact with colonized companion animals.

AVIAN PATHOGENIC E. COLI AND

HUMAN EXTRAINTESTINAL E. COLI
Evidence is increasing that some human-associated
ExPEC are related to APEC, the cause of colibacillosis,
an extraintestinal infection of poultry. Considerable
genetic similarity has been demonstrated between APEC
isolates from infected poultry and ExPEC isolates from
infected humans (32, 9195). For example, a human
sepsis-associated O111:H4-D-ST117 ExPEC strain was
closely related to known APEC strains by PFGE, virulence factor proling and phylotyping (32). A population-level association between human ExPEC and APEC
(or E. coli derived from poultry) is suggested by these
groups overlapping antimicrobial resistance patterns,
resistance genes, and virulence factors (32, 70, 72, 83,
91, 93, 95100). As for experimental evidence of crossspecies pathogenicity, several studies have demonstrated
that APEC can cause disease in mammalian models
of human ExPEC infections (e.g., the mouse model of
ascending UTI) (101, 102), and human-source ExPEC
can cause disease in certain avian disease models (72,
103).

FOODBORNE RESERVOIRS OF
HUMAN ExPEC
Foodborne transmission of food animal or retail meatassociated ExPEC has been the topic of many recent
investigations, with poultry and poultry products receiving the most attention (83, 97, 98, 100, 104106). A
review of outbreaks of ExPEC-related infections identied a sizable number of community-wide clusters (5).
Although the sources of the outbreaks were not identied, these E. coli infection clusters typically result from
point-source dissemination and food or waterborne
transmission. The proposed chain of foodborne ExPEC
transmission involves ExPEC from food animals or meat
products subclinically colonizing the human consumers
intestinal tract after ingestion of undercooked meat or
cross-contamination in the kitchen during food handling. Once an incoming ExPEC strain has established
residence in the human intestinal tract, it persists
there until circumstances favor an extraintestinal infection, e.g., sexual intercourse or urinary catheter insertion (53). The often-lengthy interval between ExPEC
acquisition and disease development, if disease ever occurs, makes transmission of ExPEC and antimicrobialresistant E. coli from external reservoirs (e.g., foods) to
humans very difcult to detect. However, although direct transmission has not been demonstrated, abundant
circumstantial evidence links E. coli recovered from food

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animal sources to human ExPEC isolates. The most

troubling aspect of these observations is the extensive
antimicrobial resistance of E. coli isolates from food
animals, particularly chickens (107, 108).
One likely contributing factor to the emergence of
antimicrobial-resistant E. coli in food animals, especially
poultry, is the large increase in human consumption
of retail chicken over the past 30 years (109). This has
led to changes in the scale and methods of food animal
production, including increased use of antimicrobial
agents for growth promotion, infection prevention, and
treatment (110), which likely has selected for and amplied multidrug-resistant ExPEC in the food animal reservoir (111). Resistant E. coli, once established in food
animals, can spread among animals and the local environment, maintaining the circulation of antimicrobialresistant ExPEC within the herd, ock, or production
facility (111).
The plausibility of foodborne transmission of antimicrobial-resistant E. coli to humans is strengthened
by the nding that antimicrobial-resistant E. coli from
chicken carcasses widely contaminate the kitchen during
meal preparation and can appear in the intestinal tract
of individuals who prepare food dishes from the carcasses (112, 113). Furthermore, volunteers fed a diet of
irradiated food exhibited markedly reduced levels of
antimicrobial-resistant intestinal E. coli, with reversion
to baseline post-intervention (114), implying that a conventional diet sustains a certain prevalence of intestinal
resistant E. coli through a steady input of resistant strains.
Thus, the available evidence, albeit indirect, strongly
supports a foodborne component to the antimicrobialresistant E. coli problem in humans.

Poultry Sources
Based on existing evidence, poultry is the food animal
source most closely linked to human ExPEC (83, 97
100, 104106). In women, UTI caused by antimicrobialresistant ExPEC has been epidemiologically linked with
high levels of self-reported chicken consumption (106).
Among different meat types, poultry generally exhibits
the highest overall levels of E. coli contamination, and
poultry-associated E. coli tend to be more extensively
antimicrobial-resistant than those from other meats
(107, 108). Poultry-associated E. coli also often possess
virulence genes characteristic of human ExPEC, suggesting a potential to cause human disease.
A 2006 study by the U.S. National Antimicrobial
Resistance Monitoring Systems (NARMS) identied 200
ExPEC isolates among 1,275 E. coli isolates from retail
meat samples. The proportion of isolates representing

ExPEC varied by meat type, being highest in ground

turkey (23.5%), followed by chicken breast meat
(20.2%), pork chops (8.3%), and ground beef (3.4%)
(115). More than half of these isolates belonged to
serogroups associated with human extraintestinal infections. Serogroup O25 (17.9%) was the most common
among chicken isolates, while serogroup O2 (36.2%)
was most common among turkey isolates. Furthermore,
42% of retail meat ExPEC isolates represented ExPECassociated phylogenetic groups B2 (25%) and D (23%)
(115). These ndings conrmed those of an earlier
study from 2002 to 2004 involving NARMS isolates,
which additionally showed that isolates from different
meat types were genetically distinct, suggesting that they
originated from the respective animal species (116).
Importantly, however, susceptible and resistant isolates
from a given meat type did not differ genetically, suggesting that the resistant isolates emerged from susceptible isolates within the different food animal hosts,
possibly from on-farm antimicrobial use (116).
Specic ExPEC lineages have been found in poultry
and poultry meat sources. Indistinguishable E. coli
O25:H4-B2-ST131 strains were identied in a human
UTI case and retail chicken meat sample in Canada (33).
Mora et al. also demonstrated similarity by PFGE and
virulence gene content between one chicken and one
human CTX-M-9-positive E. coli O25:H4-B2-ST131
isolate (117). ESBL-positive E. coli O25:H4-B2-ST131
was also recovered from poultry farms in Spain, where
human and poultry-source O25:H4-B2-ST131 isolates
exhibited moderate (75%) PFGE similarity (118). Several other studies identied antimicrobial susceptible
ST131 isolates in chickens and/or chicken meat (100,
105, 119, 120).
O11/O17/O77:K52:H18-D-ST69 likewise has been
linked to non-human reservoirs, primarily chicken (33,
101). Moreover, in an experimental study, CgA E. coli
isolates recovered in Denmark from human infections
and retail chicken meat were equally able to cause UTI
in a mouse model, suggesting that poultry-source CgA
E. coli are just as pathogenic for mammals as are
human-derived CgA strains (97).
A recent study from the Netherlands identied E. coli
(serotype: various)-A-ST10 producing CTX-M-1 ESBL
in human blood cultures and poultry, whereas TEM-52producing ST10 isolates were recovered from human
urine samples and poultry (105). A similar study from
the Netherlands also identied ESBL-producing E. coli
ST10 in chicken meat, other meat types, rectal swabs
from healthy humans, and human blood cultures (100).
A study from Canada identied multidrug-resistant

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Reservoirs of Extraintestinal Pathogenic Escherichia coli

ST10 isolates (albeit of limited PFGE similarity) in human clinical samples, chicken feces, and retail chicken
meat (121).
E. coli O1/O2/O18:K1:H7-B2-ST95 isolates with
related PFGE proles have been identied in humans
and poultry (33, 93) and, separately, in honeydew melon
and multiple human infections (33). In another study,
58% of 108 APEC and human ExPEC isolates from
serogroups O1, O2, or O18, representing diverse host
species, belonged to ST95 (70). When assessed in animal
models, O18-B2-ST95 E. coli isolates from human
neonates with meningitis could cause colisepticemia in
poultry (72); conversely, O18-B2-ST95 E. coli isolates
from cases of avian colibacillosis (APEC) could cause
neonatal meningitis in a rat model (102). This indicates
that the APEC and NMEC-associated ST95 group may
have zoonotic potential.
ESBL-producing ST117 isolates were also identied
in human and poultry reservoirs (100, 105), and genetically closely related O114:H4-ST117 strains, as
assessed by PFGE, were identied in a human UTI case
and retail chicken meat in Canada (33). CTX-M-32positive O25a:H4-D-ST648 isolates, one from a human
infection and one from a poultry source, exhibited
closely related PFGE proles (118). Additionally, human
clinical and turkey meat samples containing E. coli
ST410 were identied in Spain (122).

Pork and Pig Sources

Contamination of pork products with ExPEC has also
been reported; however, fewer studies have been conducted to date (33, 98, 123126). One epidemiologic
study found that women experiencing a drug-resistant
UTI were more likely to report frequent pork consumption (106). In another study, E. coli recovered from
pigs tended to be from phylogenetic groups A and B1
and exhibited lower overall numbers of virulence genes
compared with poultry isolates (118).
E. coli ST131 was detected among pork and UTI
isolates in one study from Denmark and Norway (127).
Additionally, O11/O17/O77:K52:H18-D-ST69 has been
linked to pork (33, 123). Multidrug-resistant and possibly related (by PFGE) ST10 isolates have been identied in human clinical samples, pig feces, and retail pork
meat (121), whereas in another study O2:H(non-motile)A-ST10 isolates were identied in pigs (118).

Beef and Cattle Sources

The evidence for a beef cattle reservoir for human
ExPEC is fairly weak. In general, the prevalence of
E. coli resembling ExPEC is low in beef cattle sources

(115, 128). One study identied a single cow isolate

that was similar by PFGE to a human O11/O17/
O77:K52:H18-D-ST69 isolate (129). The reason for
limited colonization of healthy beef cattle with ExPEC,
compared with their extensive colonization with E. coli
such as shiga-toxin producing E. coli (130), is unknown.

PUBLIC HEALTH PERSPECTIVES

Investigators of the human versus extra-human origins
of ExPEC have used both population ecology surveys
and experimental pathogenesis studies to examine host
species distribution and specicity of different ExPEC
types. What has emerged is a picture of a large and
complex group of E. coli variants, within which a small
number of highly successful lineages (in terms of virulence, prevalence, and geographic range) have become
established and account for the bulk of extraintestinal
E. coli infections in humans and some domestic animals.
The importance of these lineages is highlighted in one
recent study in which just three clonal groups (O25:H4B2-ST131, O15:K52:H1-D-ST393, and O11/O17/O77:
K52:H18-D-ST69) accounted for 19% of 500 consecutive extraintestinal E. coli isolates in 5 hospitals in Spain
in February 2009, and for 30% of multidrug-resistant
isolates (9). ST131 E. coli alone was estimated to cause
approximately 17% of extraintestinal infections in the
source populations of another surveillance program
(131). More importantly, these extraintestinal diseasecausing lineages are becoming increasingly multidrugresistant. Identication of the reservoirs and transmission pathways for these important human-associated
ExPEC groups conceivably could help to curb their
transmission and to reduce their extent of antimicrobial
resistance, thereby leading to fewer and easier to treat
human ExPEC infections.
It is increasingly clear that certain prominent ExPEC
groups can occur in non-human sources, including food
animals and meat products, although the extent of this
phenomenon, its importance to human health, and the
strength of the supporting evidence vary by source and
E. coli group. The strongest evidence for a food animal
reservoir and foodborne transmission of human ExPEC
exists for poultry and pigs, where genetically similar
ExPEC have been recovered from retail chicken, turkey,
and pork products and human infections. Although
transmission of ExPEC from food animals or retail
meats to humans has yet to be directly demonstrated,
transmission of ExPEC has been documented between
cohabiting humans, and between companion animals
and humans (49, 5153, 85).

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Manges and Johnson

Development and amplication of multidrug resistance in animal-associated E. coli is likely facilitated by

the frequent or continuous selection pressure provided
by antimicrobial use during food animal production and
veterinary medicine (132). Antimicrobial use in human
clinical medicine provides additional selection pressure
once such organisms enter the human population. Thus,
the global increase of antimicrobial resistance among
human-associated ExPEC likely has multiple ecological
origins, with important inputs from the transmission
of antimicrobial-resistant ExPEC from food animals,
companion animals, and environmental sources to humans. Each of these ExPEC reservoirs provides an
environment for amplication, followed by further amplication in humans, then possible transmission back
to these reservoirs, in a continuous feedback loop (133).
Certainly, antimicrobial stewardship is important for
reducing the selection pressure for antimicrobial
resistance in food animals and other environments
sources. Antimicrobial usage in food animals varies
widely throughout Europe, despite the 2006 European
Union antimicrobial growth promoter ban (134).
However, given the linkage of antimicrobial resistance
genes and the unavoidable need for antimicrobial use for
therapy and prophylaxis in some cases, in humans and
animals alike, stewardship is at best a harm reduction
strategy, slowing rather than preventing further emergence and spread of resistant E. coli. Recent efforts have
focused on eliminating or reducing the use in food
animals of antimicrobials classied as very important
to human medicine (e.g., extended-spectrum cephalosporins) (135), to reduce antimicrobial resistance;
however, this is not always been readily accomplished (e.
g., the U.S. Food and Drug Administrations delayed ban
on uoroquinolone use in poultry) (136). Reducing
E. coli contamination levels on meat products is another
possible intervention.
Another preventive approach deserving consideration is vaccines. Food animal-associated ExPEC lineages
possess specic traits that allow them to cause extraintestinal disease, to survive within specic reservoirs
(e.g., in avian hosts), and to disseminate widely among
human hosts. Elucidation of such factors is essential
for identifying good vaccine targets. Vaccines could be
additionally effective as a public health intervention if
directed toward the animal hosts that act as reservoirs
(137).
Ecologic studies comparing ExPEC from multiple
sources have inherent limitations, including the difculty of determining direction of transmission (from
animals to human or vice versa) and pinpointing actual

transmission events. Nonetheless, the public health

community should heed the growing body of evidence
supporting foodborne transmission of ExPEC with human pathogenic potential and should move toward
implementing policies and practices that would limit the
evolution, selection/amplication, and dissemination of
antimicrobial-resistant ExPEC from food animals and
other reservoirs to humans.
ACKNOWLEDGMENTS
Conicts of interest: We declare no conicts.

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