Biomedical Science and Research Journals | Review on Some Virulence Factors Associated with Campylobacter Colonization and Infection in Poultry and Human
Review on Some Virulence Factors Associated with Campylobacter Colonization and Infection in Poultry and Human
Introduction
Campylobacter is one of the most important four global
diarrheal diseases. It is considered to be the most common bacterial
cause of human gastroenteritis in the world causing a disease called
Campylobacteriosis. In developing countries, Campylobacteriosis
in children under the age of 2 years are especially frequent and
sometimes resulting in death [1]. Mainly C. jejuni and C. Coli
are well recognized causes of human campylobacteriososis
with symptoms ranging from mild watery diarrhea to serious
neuropathies [2]. Poultry (particularly chicken and contaminated
raw chicken carcasses) is considered to be the main source for
human campylobacteriososis. Other sources such as water, raw
milk, Cattle, sheep, pigs, cats, dogs, vehicles, rodents and insects
are known as possible sources for not only human but also poultry
Campylobacteriosis. After being colonized by Campylobacter spp.
Chicken in contrast to human, do scarcely develop pathological
lesions [3]. The high body temperature of Poultry species
provides an optimal environment for the growth of thermophilic
Campylobacter species particularly C. jejuni and C. coli which make
poultry constitute the main source of human Campylobacteriosis
[4]
Campylobacter spp. are Gram negative rods, 0.5 - 8μm long and
0.2 - 0.5μm wide with characteristically curved, spiral, or S-shaped
cells; coccal forms may be seen under sub-optimal conditions. They
generally have a single polar unsheathed flagellum at one or both
ends. The motility of the bacteria is characteristically rapid and
darting in corkscrew fashion, a feature by which their presence
among other bacteria can be detected by phase-contrast microscopy
[5,6].
On Skirrow or other blood-containing agars, characteristic
Campylobacter colonies are slightly pink, round, convex, smooth
and shiny, with a regular edge. On charcoal-based media such as
mCCDA, the characteristic colonies are greyish, flat and moistened,
with a tendency to spread, and may have a metallic sheen. Campylobacter
spp. require microaerobic conditions consisting of (5% O2,
10% CO2 and 85% N2) [7]. They neither ferment nor oxidase carbohydrates.
Energy is obtained from amino acids or tricarboxylic
acid cycle intermediates, not carbohydrates. Some species, particularly
C. jejuni, C. coli and C. lari, are thermophilic, grow optimally
at 42°C [8].
Despite over 30 years of research, Campylobacteriosis is the
most prevalent bacterial cause of foodborne infection in many
countries including in the EU and the USA [9]. As mentioned before
that poultry species are important reservoirs for the transmission
of Campylobacter species and their high body temperature provides
an optimal environment for the growth of the organism [4]. It is important
to explore further the relationships between certain Campylobacter
virulence genes and their capacity for survival in poultry
meat, and hence their contribution to the incidence of Campylobacteriosis
[10] and the large genetic diversity of Campylobacter must
be considered in epidemiological evaluations and microbial risk
assessments of Campylobacter in poultry [11,12].
As a first step, colonization of the intestine requires the ability
to move into the mucus layer covering the intestinal cells. Campylobacter
motility is conferred by the polar flagella, which together
with their ‘cork-screw’ shape allow them to efficiently penetrate
this mucus barrier [13,14]. The most important virulence factor
that has been studied and well characterized in Campylobacter spp.
was the flagellin, which is encoded by the flaA gene [15]. The global
regulator, CsrA (Carbon starvation regulator) gene, has been well
characterized in several bacterial genera and is known to regulate a
number of independent pathways via a post transcriptional mechanism,
but remains relatively uncharacterized in the genus Campylobacter
[16].
Many of virulence genetic factors connected with Campylobacter
invasiveness are placed on the pVir plasmid for example,
virB11 gene that encodes the IV secretory system protein. It has
been showed that strains with mutation in the virB11 sequence
have much lower adhesion and penetration ability in vitro in comparison
to original strains, as well as lower pathogenicity 0069n
vivo the plasmid gene virB11 [17]. One of the most important genes
responsible for Campylobacter invasion is the CiaB (Campylobacter
invasive antigen B) gene which is known to be involved in the translocation
of Campylobacter into host cells for the purpose of host
cell invasion and also plays a significant role in cecal colonization
in chicken [18]. The invasion-associated marker (iam) gene is one
of most important factors responsible for Campylobacter invasion
of host cell and this gene was first reported [19] and was detected
in 85% of invasive strains and 20% of non-invasive strains. The
pldA gene is also related to cell invasion and is responsible for the
synthesis of an outer membrane phospholipase that is important
for cecal colonization [18,20]. That gene encodes proteins associated
with increased bacterial invasion on cultured epithelial cells
[21]. Cytolethal distending toxin (CDT) in which CdtB subunit is the
active toxic unit. CdtA and CdtC required for CDT binding to target
cells and for the delivery of CdtB into the cell interior [22]. The toxin
is retrograde transported into the nuclear compartment, where
the CdtB subunit exhibits type I DNase activity. Cellular intoxication
induces DNA damage and activation of the DNA damage response,
which results in arrest of the target cells in the G1 and/or G2 phases
of the cell cycle and activation of DNA repair mechanisms, cellular
distention and nuclear enlargement, and Cdc2 and ataxia-telangiectasia-
mutated protein (ATM) phosphorylation. Cells that fail to
repair the damage will senesce or undergo apoptosis [23]. Considering
the important role that toxins have in the pathogenesis
of Campylobacteriosis and other infections, all knowledge generated
in this area will serve to propose and develop new strategies
for the control of pathogens [24]. The thermal stress response of
bacteria is mostly carried out by the induction of the expression of
heat shock proteins (HSPs). These HSPs have an important function
in thermotolerance as well as in the response to other stresses by
acting as chaperones to promote the folding of most cellular proteins
and proteolysis of potentially deleterious, misfolded proteins.
Several HSPs have been identified in C. jejuni, including the GroESL,
DnaJ, DnaK and ClpB proteins [25-28]. However, a role in C. jejuni
pathogenesis has only been demonstrated for the DnaJ protein, as
a C. jejuni dnaJ mutant was unable to colonize chickens [25]. The
importance of the C. jejuni thermal stress response is also indicated
by the link between thermoregulation and chicken colonization
through the racR regulatory protein [29] Cited by [30]. dnaJ was
detected in 100% of all chicken fecal samples examined while there
is a difference in human samples with detection rate of 98% [31].
Relatively similar results were obtained in Egypt by [32] who confirmed
these results with gene expression of dnaJ and using 23srRNA
as a housekeeping gene. On the other hand our results in human
samples agreed with [20] who detected dnaJ gene in 46% and 50%
of human C. jejuni and C. coli samples respectively although there
are some differences in results of dnaJ from chicken samples which
came in a rate of 69% and 70% for C. jejuni and C. coli respectively
[33], detected dnaJ gene in 100% of Human C. jejuni and C. coli. High
detection of dnaJ gene in chicken than human host that reported by
many authors confirmed the data that revealed importance of dnaJ
gene in broiler cecal colonization by [34]. Two-component regulatory
system, RacR-RacS (reduced ability to colonize) system, that is
involved in a temperature-dependent signalling pathway was identified
[29]. A mutation of the response regulator gene racR reduced
the organism’s ability to colonize the chicken intestinal tract and
resulted in temperature-dependent changes in its protein profile
and growth characteristics. Authors added that C. jejuni dnaJ gene
is adjacent to and under the transcriptional control of racR. [31] detected
racR gene in 98.2 and 100% of C. jejuni isolates from human
and broiler respectively [35], reported partially similar results in C.
jejuni but not C. coli. They detected racR gene in 84.9% and 95.6%
of C. jejuni from human and poultry respectively [36], detected racR
gene in 100% of C. jejuni isolated from Human diarrheal patients
in Bangladesh [37], reported racR gene in 98.3 % of C. jejuni isolates
from children’s ≤14 years who were treated for diarrhoea at
emergency rooms in north-eastern Brazil [38], detected racR gene
in 95% and 0% of human C. jejuni and C. coli respectively. And in
76% and 79% of chicken C. jejuni and C. coli respectively. Similar
results revealed by [32] in Egypt.
Infection with C. jejuni usually causes uncomplicated gastroenteritis;
however, in rare cases can lead to the Guillain-Barré syndrome
(GBS), a post infectious immune-mediated disorder of the
peripheral nerves and nerve roots [39]. The global incidence of
GBS ranges from 0.4 to 4.0 (median 1.3) cases per 100,000 people
annually, occurring slightly more often in adolescents and young
adults [40]. Results of [41] review analysis suggest that 31% of
2,502 GBS cases included in this review are attributable to Campylobacter
infection. Molecular mimicry between lip oligosaccharides
(LOS) present on the cell wall of C. jejuni and gangliosides found in
the human nervous system is thought to play a critical role in the
pathogenesis of C. jejuni-related GBS [42]. The wlaN, cgtB and waaC
are LOS (lipo-oligosaccharides) associated genes while wlaN and
cgtB are involved in β-1,3 galactosyltransferase production. These
two genes are associated with waaC gene which encodes heptosyltransferase
I [43]. The waaC gene, which encodes heptosyltransferase
I, is responsible for transferring the first l-glycerod- manno-
heptose residue to the inner core of LOS [44]. The wlaN gene,
which encodes a beta-1,3 galactosyltransferase, is responsible for
biosynthesis GM1-like structure whereas cgtB (which encodes another
beta-1,3 galactosyltransferase) catalyzes the biosynthesis of
the carbohydrate moieties analogous to GM2 [45]. Sialyltransferase
encoded by the cst-II gene in C. jejuni is associated with risk of
developing GBS [46]. On the other hand, the cst-II gene has been
linked to the invasiveness of C. jejuni for intestinal epithelial cells
[47]. C. jejuni gene ggt encoding the periplasmic gamma-glutamyl
transpeptidase (GGT) seems to play a pivotal role in the enteric colonization.
GGT has been shown in chicken model to be important
in long lasting gut colonization, and in vitro it has been shown that
GGT plays a significant role in C. jejuni-mediated apoptosis [48,49]
detected cst-II and ggt genes in 83.6% and 32.7% of 55 examined
Campylobacter jejuni human origin isolates and 40% and 5.5% of 55 Campylobacter jejuni broiler meat origin isolates in Chile [50],
detected cgtB, wlaN and waaC genes in 7.69%, 30.77% and 57.69%
of isolates respectively in Bangladesh [51], detected wlaN and cgtB
in 20% and 6.7% of 30 C. jejuni isolates from Patients with Diarrhea
in Rosario, Argentina.
Conclusion
Campylobacter epidemiology results should be liked with its
virulence gene characterization. Although the molecular basis
of pathogenicity of Campylobacter has not been fully elucidated,
several virulence factors have been identified based on in vitro
and in vivo studies. For example, flaA, cadF, CsrA for adhesion.
iam, virB11, ciaB and pldA (invasion). CDT (CdtA, CdtB and CdtC)
(cytotoxicity). dnaJ (heat shock protein). racR (reduced ability to
colonize). cgtB, waaC, cstII, wlaN & ggt (ganglioside mimicry).
To view fulltext of article:https://biomedgrid.com/fulltext/volume3/review-on-some-virulence-factors-associated-with-campylobacter-colonization-and-infection-in-poultry.000717.php
Comments
Post a Comment