is a Gram-negative,
rod-shaped bacterium and a member of the
Enterobacteriaceae family of Proteobacteria that
causes a broad range of gastrointestinal
syndromes ranging from acute enteritis and
enterocolitis to mesenteric lymphadenitis
Since Y. enterocolitica
predominantly causes zoonotic infections,
it is commonly found in swine, cattle, sheep,
horses, dogs, cats, and rodents (De Berardis
et al., 2004). Humans may be exposed by
consuming contaminated foods, specifically
undercooked pork products or unpasteurized milk
(Trosky et al., 2008).
Additionally, agricultural runoff may
contaminate drinking water and spread to humans
if ingested. Transmission may also occur through
transfusion of contaminated blood. However, in a
large number of human cases, the route of
exposure generally remains unknown.
Figure 1. A
photomicrograph of Yersinia enterocolitica
using Flagella staining technique.
Approximately one week after
infection, symptoms develop in the form of
bloody diarrhea, fever and abdominal pain (De
Berardis et al., 2004). These symptoms
usually last for one to three weeks, and can be
characteristic of a number of gastrointestinal
terminal ileitis (Trulzsch et
al., 2007). Due to the similarities in
symptoms, mesenteric lymphadenitis is often
misdiagnosed as acute appendicitis. Further
complications may arise with the spontaneous
manifestation of monarticular arthritis, which
may occur one to six months after the initial infection
(De Berardis et al., 2004).
There are a few factors which
may increase or worsen the incidence of Y.
enterocolitica infection. Young children
demonstrate increased rates of infection
resulting in diarrhea and abdominal pain,
whereas the elderly are more susceptible to
developing monarticular arthritis. Since Y.
are siderphilic, individuals with iron
overloads, such as hemochromatosis, are
predisposed to systemic infection or focal
abscess formation in the spleen and liver (Oellerich
et al., 2007). Fatal septicemia may
also occur more frequently in patients with
alcoholism, cirrhosis, diabetes, immune
depression, or neoplasias (Matsumoto & Young,
Diagnosis of a Y. enterocolitica
infection may occur via stool or blood cultures.
Y. enterocolitica grows well on most
enteric media, however, most commonly stool
samples are incubated at 25°C on
Cefsulodin-irgasannovobiocin (CIN) agar for 18
to 20 hours (Bottone, 1997). This media is
highly selective for Y. enterocolitica,
and a positive diagnosis can be seen with the
growth of small colonies with red centres. The
detection of bacteria in bloodmay occur via an
ELISA specific for IgA, IgG and IgM antibodies
produced in the presence of Y.
enterocolitica (Bottone, 1997).
Although there is no vaccine
available to date, aggressive antibiotic therapy
is effective at eliminating Y.
enterocolitica post-infection (De Berardis
et al., 2004). Common antibiotics
include ampicillin, gentamicin, criprofloxacin,
amoxicillin (Figure 2), cefuroxime, imipenem, and
cefoperazone (Bottone, 1997).
However, the best method of controlling the
spread of disease is prevention. These
preventative measures include avoiding high risk
foods, such as undercooked meats, unchlorinated
water, and unpasteurized milk. Also, washing
soap and water after contacting animal or human
feces is essential for defence against Y.
enterocolitica (De Berardis et al.,
Figure 2. Chemical structure
The oral infective dose of
Y. enterocolitica has been found to be
108 to 109 organisms/mL (De Berardis et al.,
2004). From this small culture, the bacteria are
able to proliferate
extracellularly to form microcolonies within the
small intestine. Although Y. enterocolitica
possess flagella, the bacteria are motile at
25°C, but not at 37°C (De Berardis et al.,
2004). This suggests that upon introduction into
humans, Y. enterocolitica must obtain
another method of transportation to disseminate
throughout the body.
To overcome the mucosal
barrier in the small intestine, Y.
enterocolitica utilize M cells for
3). This is achieved through the
exploitation of Invasin (Inv) and Yersinia
adhesion A (YadA). Invasin facilitates adhesion
to β1 integrins, which are expressed on M cells
(Roppenser et al., 2009). Further
adhesion occurs through extracellular matrix
bridging between YadA, collagen and fibronectin
(Oellerich et al., 2007). Together,
these virulence factors allow Y. enterocolitica
to permeate the intestinal cells, where the
bacteria can then invade the Peyer’s patches, or
spread systemically to the spleen, liver, or
mesenteric lymph nodes (Wiedig et al.,
2005) (Figure 4). Abscess formation in the Peyer’s patches,
spleen and liver are due to the presence of a
single bacterium. This bacterium may become
lodged in the capillary vessels, and upon
replication cause a monoclonal abscess (Oellerich
et al., 2007).
Antigens transported across the intestinal
epithelium by M cells are delivered to the
Peyer's patches. Click to enlarge.
Figure 4. The
Peyer's patches are visible as a small bulge in
the side of the small intestine.
possess a 70 kb DNA plasmid, which is essential
to its virulence. This plasmid encodes a Type
III secretion system (T3SS) and effectors known
as Yersinia outer proteins (Yops). The T3SS
consists of a base structure, and a needle-like
protein used for the injection of effectors into
the target cell (Koberie et al., 2009).
Y. enterocolitica contain six Yops (YopH,
YopE, YopO, YopM, YopJ and YopT) which become
activated once inside the target cell. YopH,
YopT, YopO and YopE are capable of disrupting
the formation of actin microfilaments among
macrophages and neutrophils. This prevents the
phagocytosis of the bacterium. YopE is also
regulating the amount of effectors injected into
the target cells (Trosky et al., 2008).
YopM does not contain catalytic activity, but
acts as a scaffold protein once in the nucleus.
Finally, the function of YopJ is to increase
programmed cell death in the infected cells,
thereby suppressing the immune system and
prolonging the survival of the bacterium (Koberie
et al., 2009). A summary of the effects
of YOPs are illustrated below; take note on how
YopP blocks the phosphorylation cascades (MAPK &
NFkB pathways) and TNFα production, causing
apoptosis to occur via the caspase pathway
Effects of Yersinia YOPs on inhibition
of the inflammatory response needed to resist
infection. Click to enlarge.
The injection of effectors
into the target cells induces the MHC class I
pathway, as intracellular antigens are present.
This in turn induces CD8+ T cell
responses (Wiedig et al., 2005). Also,
the complement cascade may become activated in
the presence of LPS found in the outer membrane
of these Gram-negative bacteria. However, Y.
enterocolitica are able to efficiently
resist complement and opsonization by utilizing
the bacterial outer proteins YopA and Ail (Kirjavainen
et al., 2008). The unique ability of
Y. enterocolitica to effectively
suppress the immune system has contributed to
its increased virulence within the human body.
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