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Campylobacter concisus: an emerging pathogen of the gastrointestinal
tract
Taghrid Istivan1 Peter Ward
3 and Peter Coloe
1,2
1School of Applied Sciences & Health Innovation Research Institute, RMIT University, Melbourne, Australia 2Science Engineering and Health College, RMIT University, Melbourne, Australia 3Microbiology Unit, Austin Pathology, Austin Health, Melbourne, Victoria Australia
This chapter explores the role of Campylobacter concisus, as an emerging pathogen of the human gastrointestinal tract.
This bacterium is a Gram negative curved rod that composes part of the gingival flora of the human oral cavity. The
association of C. concisus with human periodontal diseases and gingivitis has been reported since the 1980s. However in
this decade the focus on this species has shifted to its role in gastroenteritis in children and immunocompromised adults, in
addition to its association with inflammatory bowel diseases. In particular the chapter focuses on the association of C.
concisus with oral and intestinal infections, and on recent developments in applied molecular detection techniques to
highlight the molecular diversity and virulence factors of this emerging pathogen.
Keywords: Campylobacter concisus; gingivitis; periodontitis; gastroenteritis; Inflammatory Bowel Diseases;
hemolysin(s); adhesion; molecular detection; emerging pathogen; molecular diversity
1. Campylobacter concisus: The microorganism
Campylobacter concisus is a fastidious, hydrogen-requiring, slow growing organism that is found in the human oral
cavity and occurs mostly in periodontal pockets of diseased gums. It has been characterised as an opportunistic
microorganism associated with gingivitis, periodontitis and gastroenteritis [1, 2].
Tanner et al. [3] first described C. concisus (Latin concisus meaning concise) as small asaccharolytic, non-
pigmenting gram-negative rods isolated from gingival crevices of persons with gingivitis and periodontitis. In 1984,
Holdman et al. [4] renamed a group of organisms that derive their energy by reduction of fumarate or nitrate with
formate or with hydrogen as Campylobacter concisus. These microorganisms were previously thought to be human
isolates of "Vibrio succinogenes". This species was reported within a group called “anaerobic vibrios” to be small,
Gram-negative, asaccharolytic rods, which grow in broth media supplemented with formate and fumarate [5], are motile
with one or two polar flagella, and show a chemotactic response to formate in a concentration reported to be present in
dental plaque [6].
The first isolation of C. concisus from a non-oral clinical specimen was reported in 1985 from a foot ulcer wound for
a patient with diabetes mellitus [7]. However, until recently the pathogenic potential of this bacterium was uncertain as
it has been identified in faecal samples from both healthy and diarrheic patients [1, 8-10]. In most diarrheal cases, C.
concisus was isolated as the only potential intestinal pathogen, which implies that it is a primary pathogen. Since C.
concisus is fastidious and has low biochemical activities, its identification is problematic by the conventional
phenotypic techniques. In recent years the application of the “Cape Town protocol”, which involves membrane
filtration onto antibiotic-free culture media [11], has enhanced the rate of C. concisus isolation from clinical samples.
Also, the wider use of molecular detection techniques [12-13], has resulted in a higher number of reported C. concisus
cases from gastric and extra-gastric infections.
Unlike most other Campylobacter spp., this bacterium does not have any known animal host and there are no reports
on its isolation from healthy animals. A recent study to determine quantifiable levels of Campylobacter spp. shed from
domestic pet dogs, using a culture-independent approach, reported the detection of C. concisus in faecal samples from
diarrheic dogs, but failed to detect them in healthy dogs [14].
2. Campylobacter concisus of the human oral cavity
2.1. Campylobacter spp. as a part of oral cavity microbiota
A study by Macuch and Tanner [15] suggests that C. concisus, C. showae, C. curvus and Campylobacter X colonize the
oral cavity more frequently than might be expected for transient species and may represent opportunistic pathogens
under certain medical conditions. At least seven Campylobacter species have been identified from different subgingival
sites, with C. rectus identified as a periodontal pathogen. Other Campylobacter spp. or taxa that have been isolated
from oral sites include C. concisus, C. curvus, C. showae, C. showae-like, C. sputorum and Campylobacter X [15].
Campylobacter spp. other than C. rectus and C. gracilis have rarely been detected in periodontal samples, which could
_______________________________________________________________________________________
be related to their presence below the detection limit of microbiological assays and to incomplete genotypic and
phenotypic strain characterization [16].
2. 2. The possible role of C. concisus in gingivitis and periodontitis
To date there is relatively little information on the exact involvement of C. concisus in periodontal disease, which may
reflect difficulty in its isolation [17]. C. concisus has been linked to periodontal disease since the early 1980’s [3, 18].
The species has been demonstrated in gingivitis in young adults. An investigation on the composition of the
subgingival microbiota in children with primary dentition aged 4-5 years showed that C. concisus was present in low
numbers generally and was isolated in greater numbers around molars than incisors [19]. In children aged 7-8 years
with a mixed dentition, C. concisus was found more frequently in plaque from permanent teeth than plaque from
deciduous teeth [20], and it was associated with bleeding gum sites in both groups [19-20]. This organism has been
identified as a pathogen in early-onset forms of periodontal disease and has been associated with progression of the
disease especially in bleeding sites [20-22]. C. concisus has also been associated with the progression of periodontitis
in adults [23-24], and also patients with periodontal disease showed a greater antibody response to this bacterium
compared to healthy subjects [25]. C. concisus was grouped into one of the six successional complexes that are
believed to be involved in periodontal diseases [26].
3. Campylobacter concisus from non-oral origins
3.1. Etiology and prevalence of C. concisus in gastroenteritis
C. concisus has been linked to gastroenteritis, particularly in infants from 0-35 months of age and has been isolated
(mainly by culture filtration technique) from children with diarrhoea in Europe, Australia and South Africa [8-11]. The
reported isolation rates for C. concisus varies widely between laboratories which could be influenced by isolation and
identification methods, geographical factors, sources and routes of transmission, as well as numbers of faecal samples
tested and differences in study population regarding age group and health conditions [27]. The isolation rate of C.
concisus from stool samples of paediatric patients with diarrhoea, was reported to be 5% of the total samples tested over
a ten year period at Cape Town in South Africa, the second highest rate after C. jejuni, when the stool filtration
technique on an antibiotic free blood agar was introduced [2]. However, when a similar technique was used to isolate
H2-requiring Campylobacter spp. at the Royal Children’s Hospital (RCH) in Melbourne, Australia, an isolation rate of
3% was reported for C. concisus. Most of the patients were reported to be 2-30 months of age with gastrointestinal
symptoms including diarrhoea, vomiting, fever, and abdominal pain [28, 29].
A study undertaken in Copenhagen, Denmark [8] reported a total of 52 C. concisus strains isolated from 1,376
diarrheal cases (>3%), particularly in young children (<24 months) and the elderly (> 60 years). These finding were
followed by a study from another Danish research group [30] on the prevalence of C. concisus in diarrhoea of
immunocompromised patients. It was reported that C. concisus was the most prevalent Campylobacter spp. isolated,
being responsible for 49% (110/224) of all campylobacter isolates in immunocompromised patients, and that the
isolation rate was higher in late summer with a smaller peak in spring [30]. Seasonal variations and peak patterns in
spring and summer were similarly found in gastroenteritis cases caused by C. concisus in Australian children at a study
conducted at RCH in Melbourne (P. Ward, unpublished).
3.2. C. concisus in Crohn’s disease patients
A recent study in Sydney, Australia [31] on 114 colonic biopsies from children with Crohn’s disease (CD) attending
Sydney Children's Hospital, found that a significantly higher percentage of Campylobacter species (82%), and in
particular Campylobacter concisus (52%), were detected with high titre of antibody against C. concisus as compared
with controls. This finding is of particular significance given that the pathogenic potential of C. concisus and other non-
jejuni Campylobacter species has recently begun to be recognised [31, 32].
3.3. C. concisus from extra-oro-intestinal infections
C. concisus was recently detected in the synovial fluid of patients with campylobacter-associated reactive arthritis [33].
Reverse transcription PCR amplification of specific 16S rRNA sequences was applied on synovial fluids from arthritis
patients, which revealed the presence of transcriptionally active skin and gut commensals including two different C.
concisus strains. In addition C. concisus has been detected by PCR in 4 of 7 endoscopic biopsy samples from patients
with Barrett’s esophagitis (BE), but in none of the controls [34]. A more recent study on cases of extra-oro-intestinal
abscesses reported C. concisus detection in a 65-year-old man with a history of maxillary sinus carcinoma, whom later
developed a brain abscess due to polymicrobial flora [35]. As Campylobacter spp. including C. concisus are rarely
_______________________________________________________________________________________
isolated from extra-oro-intestinal origins, the pathogenic role of this organism in such polymicrobic infections is to be
elucidated.
4. Isolation and identification of Campylobacter concisus in clinical samples
4.1. Culture and Microscopy
The filtration method combined with selective culture [8] or growth on an antibiotic free medium [2], are the most
common methods for the isolation of this bacterium from stool samples of enteritis patients.
All C. concisus strains are slower in their growth than C. jejuni and they require hydrogen-enriched environment, in
addition they grow better at 37ºC than at 42ºC. Faecal material or other samples can be cultured by preparing a 1:2 to
1:10 suspensions in phosphate buffered saline (pH 7.4) or in heart infusion broth. Four or 5 drops of the suspension are
placed on a 0.65µM pore size cellulose acetate filter placed on the surface of a Petri dish of Columbia blood agar base
containing 5% horse or sheep blood. After the fluid has soaked through, within approximately 10 min, the filter is then
removed and discarded. Once any remaining visible suspension has soaked into the agar the plates should be incubated
at 37C in an atmosphere of 7% hydrogen, 7% carbon dioxide 7% oxygen and the balance of nitrogen. This can be
achieved either by using the evacuation replacement procedure by evacuating an anaerobic jar to approximately -0.7 bar
and then re-gassing to atmospheric pressure with a gas mixture of 10% hydrogen, 10% carbon dioxide and a balance
nitrogen, or by the use of an anaerobic gas pack in an anaerobic jar without a catalyst (if using gas packs that require
catalyst). The plates should be incubated for 3-5 days before the jar is opened.
C. concisus colonies are small (1-2 mm), round, entire, greyish and semitranslucent. Microscopy of wet mounts of
this bacterium in PBS or heart infusion broth reveals very small, slightly curved rods with rapid darting motility. Gram
staining shows small fine curved to spiral Gram negative rods. Like other Campylobacter spp. C. concisus can form
long rods and may also be found in coccoid forms as indicated in (Fig.1).
Fig. 1° Gram-stained smear for a 5 days old culture of Campylobacter concisus, presenting both the normal short curved, and the
long curved bacterial cells from the same colony. Magnification 1000x [9].
4.2. Conventional phenotypic identification
Suspected C. concisus colonies can be identified by conventional phenotypic and biochemical tests for Campylobacter
spp. including colony morphology, organism motility, organism morphology by Gram stain, oxidase, catalase,
dependency on hydrogen for growth, H2S production, indoxyl acetate hydrolysis, DNase production, susceptibility or
resistance to specific antibiotics, hippurate hydrolysis, nitrate reduction and growth on MacConkey agar [10, 36, 37].
Sensitivity to cephalothin and nalidixic acid, the growth of cultures at 25C° and 42C°, and colony colour, are of little
use in differentiation between C. concisus and C. mucosalis [38], and to differentiate strains from both species. A
diagnosis based only on biochemical reactions and susceptibility tests misidentified a C. concisus strain, isolated in
almost pure culture from stool of a young male with a chronic lymphatic leukaemia, as C. mucosalis. The isolation was
later identified as C. concisus by conducting a 16S rRNA sequencing [39].
4.3. Molecular Detection and Characterisation
In 1989 Vandamme et al. [1] used SDS-PAGE protein profiles, immunotyping and DNA:DNA hybridization, to
identify the 22 C. concisus EF group strains isolated from patients with gastroenteritis. These strains had a DNA
binding value of at least 42% with the C. concisus type strain, showing a degree of genomic heterogeneity. This study
concluded that C. mucosalis is more closely related to C. concisus than any other Campylobacter spp. [1]. However
later molecular studies indicated that the H2-requiring Campylobacter species appear to be closely related
phylogenetically [40, 41]. C. concisus, C. showae, C. rectus, C. curvus, C. gracilis, C. sputorum and C. hominis all
_______________________________________________________________________________________
belong to the first distinct group of the 16S rDNA sequences of Campylobacter spp. phylogenic tree as determined by
neighbour-joining analysis [41].
The first C. concisus-specific PCR assay, based on a target sequence of 23S rDNA was developed by Bastyns et al.
in 1995 [12]. Subsequently, Engberg et al. [8] reported consistently obtaining a PCR product of 308 bp for the
amplified gene fragment from type strains of C. showae and Wolinella succinogenes in preliminary set up experiments.
Matsheka et al. [13] indicated too that this method did not identify C. concisus consistently, because of the genotypic
heterogeneity within the species, and reported developing a more reliable and rapid PCR assay which is currently
regarded more specific for the molecular detection of C. concisus by using primers annealing to the extremities of a
1.6kb DNA fragment isolated from a C. concisus genomic library. This PCR assay was considered specific for C.
concisus as specific products were not obtained from any other Campylobacter spp. [13]. Gorkiewicz et al. [42]
suggested that partial 16S rRNA gene sequencing is an effective and rapid procedure for the specific identification of
Campylobacter spp. including C. concisus. Hence, as the complete genome sequence of C. concisus 13826 (NCBI
Reference Sequence: NC_009802.1) has been deposited in the Gene Bank databases in late 2007, many PCR detection
assays have been developed recently for the molecular detection of this species in clinical samples [33].
4.4. Antimicrobial Resistance
There is a scarcity of reports on susceptibility testing and of resistance patterns of C. concisus. There is also a lack of a
standard validated method for simple use in a diagnostic laboratory. Disc diffusion testing is not reliable for this slow
growing organism and the dilution antimicrobial test is too cumbersome. Two recent studies successfully used E-tests
to generate some MICs for Campylobacter spp. [43, 44]. Unfortunately, there are no interpretive data and breakpoints
for determining resistance and susceptibility of C. concisus in the Clinical and Laboratory Standards Institute (CLSI)
approved standards. Aabenhus et al. [43] reported resistance rates among 109 isolates of C. concisus, which were 2%
for ampicillin, 5% for ciprofloxacin, 0% for ceftriaxone, 7% for erythromycin and 3% for tetracycline. Vandenberg et
al [44] tested the antibiotic resistance of 20 C. concisus strains. All had a MIC of ≤ 1 mg ampicillin/L, 100% had
gentamicin MICs of ≤ 4 mg/L, and 95% had ciprofloxacin MICs of ≤ 1 mg/L (1 had a MIC of 32mg/L). Tetracycline
and erythromycin MICs were ≤ 4 mg/L in all isolates. Only 80% were reported as resistant to naladixic acid with MICs
of 32 or more. This suggests that a reduced MIC to ciprofloxacin would be expected and hence potential treatment
failure if ciprofloxacin was used to treat infection.
4.4.1. Should C. concisus be treated with antibiotics?
Although there are recent reports of C. concisus involvement in periodontal disease, diarrhea and Crohn’s disease [15-
16, 30-35, 45], its isolation in many cases is not associated with enteric disease. Thus, more data and evidence are
needed before the role of antibiotics can be assessed. If antibiotics are used, particularly in the immunocompromised it
is most likely that agents found to be successful in treating of other Campylobacter spp. would be successful also with
C. concisus. Therefore, it would be wise to check ciprofloxacin MICs before initiating treatment and to check clearance
and MICs in isolates where clinical response is slow. As a high proportion of C. concisus isolates are resistant to
naladixic acid, it may be that ciprofloxacin resistance or poor response to such therapy would result from accumulating
mutations in the gyrA gene. It was reported [46] that the use of veterinary specific fluoroquinolones in chickens
generated a rapid increase in the ciprofloxacin MICs of C. jejuni (from 0.250 mg/mL to 32 mg/mL). This increase
appeared within the treatment time frame and persisted long after treatment was stopped [46]. Therefore, as
fluoroquinolones are commonly used to treat patients with Campylobacter spp. infections, the emergence of resistant
strains will limit the therapeutic usefulness of these drugs.
5. Campylobacter concisus: a heterogenous species
Little is known about C. concisus mode of transmission, reservoir, and pathogenesis due to the lack of well established
typing procedures and virulence related studies [47]. C. concisus is known to be heterogeneous; therefore a definitive
identification of this species is complex because of its phenotypic diversity. The lack of well-documented methods that
can effectively discriminate C. concisus genotypes, as well as the lack of extensive studies for virulence factors has
hindered the findings on whether C. concisus strains colonising the oral cavity represent a single genotype that is also
recovered from cases of diarrhoea and from healthy individuals [15, 27, 37]. Protein electrophoresis and DNA-DNA
hybridization revealed that C. concisus is a heterogeneous species with many genotypic subgroups.
5.1. Protein profiles of C. concisus clinical isolates:
SDS-PAGE protein profiles were first used to highlight species differences between C. concisus and other small
asaccharolytic, non-pigmenting Gram-negative rods of the human oral cavity by Tanner et al. in 1986 [48]. Analysis of
SDS-PAGE protein profiles of 19 C. concisus RCH clinical strains isolated from gastroenteritis cases in children in
addition to reference strains ATCC 51561 and 51562 was conducted by our team [29]. The study assigned these strains
_______________________________________________________________________________________
into more than five groups according to their protein profiles, and concluded that the protein profiles of whole cell
lysates (WCL) and outer membrane proteins (OMPs) for the strains were divergent, but they had no similarity with the
protein profiles of C. mucosalis ATCC 43264 [29]. The WCL protein profiles (Fig. 2 a) and OMP profiles (Fig. 2 b) for
C. concisus clinical strains (Lanes 2-9, Fig. 2 a & b) and C. mucosalis ATCC 43264 (Lane 1, Fig. 2 a & b) demonstrate
the diversity of the protein profiles within C. concisus isolates, yet these profiles are distinguishable from C. mucosalis
ATCC 43264 profile. The figure also shows the significant similarity between the protein profiles of at least 3 C.
concisus clinical strains (Fig. 2, lanes 5-7, in a, and 4-6 in b).
5.2. Molecular typing of C. concisus strains
Understanding the epidemiology of C. concisus was hampered by the lack of an established genotypic identification
tool. Only limited genotyping studies have been carried out on C. concisus. At present, this species is known to
comprise at least four genomospecies, which are phenotypically indistinguishable, but genetically divergent by DNA
hybridization, AFLP analysis, PFGE, and by PCR amplification [1, 43, 37, 49, and 9 respectively]. A modification of
the PCR amplification of the 23S rDNA region in C. concisus [12] assigned 21 C. concisus strains into two molecular
groups (genomospecies) [29]. This modified 23S rDNA PCR method was applied on 39 C. concisus isolates from
Denmark and the strains were also assigned into 2 definitive genomospecies [37]. The ratio of C. concisus isolates from
Australia assigned to the first group (genomospecies A) was 71.8% as compared to 33.3% of the isolates from
Denmark. And the ratio for the second group (genomospecies B) within the isolates from Australia was 28.2% as
compared with 66.7% for the isolates from Denmark (29, 37 respectively). These results indicate that a true difference
in geographical distribution of C. concisus genomospecies related to gastroenteritis might exist, which needs to be
further investigated.
Aabenhus et al [43] used Amplified Fragment Length Polymorphism Analysis (AFLP) to investigate the genetic
diversity of the species, and the results were correlated with clinical data [43]. All C. concisus strains gave unique
AFLP profiles, and numerical analysis of these data distributed the strains among four genomospecies. The strains from
the 2nd
genomospecies were more frequently isolated from immunocompetent patients and/or patients without
concomitant infections that presented with fever, chronic diarrhoea, and gut inflammation. It was indicated too that
only strains from this genomospecies were correlated with bloody diarrhoea [43]. This was also confirmed when the
same AFLP typing system was applied on South African isolates from paediatric gastroenteritis patients (Stephen On,
personal communication). The current AFLP analysis data show that C. concisus contains at least four distinct
genomospecies that may exhibit differences in their spectra of virulence potential [43]. The occurrence of bloody
diarrhoea in cases with a particular genomospecies, suggest that a specific toxin which is produced by these strains may
be involved.
a b
Fig. 2° SDS-PAGE protein profiles for C. concisus whole cell lysates (WCL) in a, and outer membrane proteins (OMPs) in b. The
protein profiles in lane 1 are for C. mucosalis (ATCC 43264). Protein profiles in lanes 2-9 are for C. concisus clinical strains isolated
from children with diarrhoea in Melbourne, Australia [9].
_______________________________________________________________________________________
6. Virulence factors in Campylobacter concisus
To date, only limited studies on the potential pathogenicity of this species have been conducted [9]. Adhesion and
invasion assays performed on four of RCH C. concisus isolates showed that three of the four strains were adhesive and
invasive to INT407 cell line [28]. These four isolates were among other RCH clinical strains reported to be haemolytic
on different types of erythrocytes [29, 50]. CDT-like effect on Vero cells was also reported in 90% of 39 C. concisus
isolates from Danish patients with diarrhoea [37].
6.1. Hemolysins of C. concisus
Cell- associated and secreted hemolytic activities have been reported in C. concisus clinical isolates [29, 50]. Both
types of hemolysins have been reported in other pathogenic Campylobacter spp. such as C. coli and C. jejuni [51].
The detection and characterisation of a stable, cell-associated hemolysin was reported in 21 C. concisus clinical strains
[29, 50]. This hemolysin was characterised as a calcium-dependent, cytolytic, outer-membrane phospholipase A
(OMPLA) [9]. The hemolytic fraction of the extracted membrane-bound phospholipase A induced vacuolation and
cytolysis of Chinese Hamster Ovary (CHO) cell line (Fig. 3 b & c respectively).
a b c
Fig. 3° Phase contrast photomicrographs for Chinese Hamster Ovary (CHO) cell line treated with a crude haemolytic extract (HE) of
C. concisus. Cells were cultured in a 24-well plate until they reached confluent stage in (a). The confluent growth was then treated
with diluted HE in (b), or with concentrated HE in (c). After incubation at 37oC under a 5% CO2 atmosphere, cells were examined
by phase-contrast microscopy at 16 h. C. concisus HE caused detachment of the confluent layer and induced vacuolation and
cytolysis of CHO cells (b & c respectively).
Further investigations to detect possible genes related to the membrane-bound hemolysin in C. concisus resulted in
the identification of a pldA gene, the structural gene encoding for phospholipase A (accession no. AJ786391). The
nucleotide sequences of the pldA gene in different C. concisus strains had >98% similarity with the pldA gene of C. coli
[29, 50], and the nucleotide sequence of the pldA gene is highly conserved in Campylobacter spp. indicating
interspecies conservation of this gene. This is not unexpected, as the pldA gene is highly conserved in other Gram-
negative bacteria too [52]. When the nucleotide sequences of the flanking regions of the pldA gene were analysed, it
revealed that the pldA gene in C. concisus is located upstream of the ceuB gene [9]. A similar structure of the pldA gene
upstream of the ceuB and the ceuC genes which are associated with the enterochelin transport system has been reported
in both C. coli and C. jejuni genomes. However, no homolog for the pldA gene was found in the complete genome
sequence of C. concisus 13826 complete genome (Accession NC_009802), indicating that the pldA gene is missing in
this strain, probably by deletion at an earlier evolutionary stage, or perhaps the Australian isolate/s has acquired the
pldA gene from a related species in more recent times.
The 3D structure for the C. concisus PLA molecule in (Fig. 4 a) indicated that it has a β-barrel structure with a
significant resemblance to the PLA protein molecule of C. coli (Fig. 4 b) and to the 12-β-stranded architecture proposed
for OMPLA molecule of E. coli (Fig. 4 c) [9, 50]. Recent studies have indicated a possible role of pldA gene product
in bacterial colonisation and virulence of C. coli and C. jejuni pathogenic strains [53, 54]. Similar research with a pldA
mutant in Helicobacter pylori suggested that the H. pylori phospholipase has a role in colonisation of the gastric mucosa
and possibly tissue damage after colonisation [55].
_______________________________________________________________________________________
a b c
Fig. 4° The 3-D β-barrel monomer structure of C. concisus OMPLA in a, of C. coli in b, and of E. coli in c.
http://www.ncbi.nlm.nih.gov/entrez/query [9, 52].
A labile secreted hemolytic activity was detected in fresh cultures of C. concisus clinical strains. This hemolytic
effect was neutralised by incubating the hemolytic extract (HE) with C. concisus specific antiserum raised against
whole cell extracts of a C. concisus clinical strain [50]. The influence of iron on hemolytic activity was investigated to
determine the possible presence of iron-regulated hemolysins in C. concisus as previously reported in other Gram
negative bacteria. Ferrous ions had a significant effect on hemolytic activity of C. concisus [50]. Hemolysin synthesis
is known to be regulated by iron in Gram negative pathogens such as C. jejuni and V. cholerae [56-57], therefore the
presence of iron-regulated hemolysin(s) in C. concisus suggests a potential role for this hemolysin as a virulence factor
in the disease caused by this microorganism. Furthermore, the neutralisation of the secreted hemolytic activity when it
was incubated with C. concisus polyclonal antiserum indicated the immunogenic effect of the hemolysin(s) [9, 50].
The sequencing of C. concisus hemolytic inserts from C. concisus genomic library identified genes similar to those
present in other Campylobacter spp. but with no relation to hemolytic activity [50]. The nucleotide sequences of the
hemA and the proS genes (Accession FM178561) have 82% similarity to the genome sequence of C. curvus 525.92
(Accession CP000767). The detection of both secreted and membrane-bound hemolytic activities in C. concisus
indicated the presence of certain virulence factors in this opportunistic pathogen. Furthermore, the determination of
gene clusters with nucleotide sequences similar to genes that are known to influence hemolytic activity and virulence in
other Campylobacter spp., in addition to the full characterisation of the C. concisus pldA gene and its role in the
production of the hemolytic phospholipase A activity indicate the possible pathogenic role of this bacterium in
gastroenteritis.
7. Conclusion
The emergence of C. concisus as a human pathogen has been slow. However, it is now becoming more obvious that
this bacterium can colonise people, and has a number of virulence factors that are shared with other Campylobacter spp.
Hence, with reports of disease associations, further clinical and laboratory research is needed to clearly define the role
that C. concisus and some of its cellular components might have in relation to the colonisation and pathogenesis.
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