Campylobacter concisus and inflammatory bowel disease

Table 1 Detection of Campylobacter concisus in samples obtained from healthy individuals

Samples	Cultivation of C. concisus	Detection of C. concisus DNA by PCR
Human saliva	75%	97%-100%
Human feces	0%-2.8%	33%
Human intestinal biopsies	0%	2%-38%

Data shown in this table were obtained from references 5-10 and 17-21. To date, no studies have detected Campylobacter concisus (C. concisus) in samples obtained from healthy animals. The collective data suggest that humans are the natural host of C. concisus and the oral cavity is the primary colonization site. PCR: Polymerase chain reaction.

Table 2 Genetic relatedness of enteric and oral Campylobacter concisus strains

Enteric C. concisus strains from patients with IBD	Genetically related C. concisus strains
A strain isolated from intestinal biopsies of patient No. 1	An oral strain from patient No. 6
A strain isolated from intestinal biopsies of patient No. 3	An oral strain from patient No. 3 (identical)
A strain isolated from luminal fluid of patient No. 3	An oral strain from healthy No. 1

Data shown in this table were obtained from reference 13. The genetic relatedness was assessed based on the sequences of six housekeeping genes. These data provide evidence showing that Campylobacter concisus (C. concisus) strains colonizing the intestinal tract of patients with IBD originating from either the patient’s own oral C. concisus strains or oral C. concisus strains from other individuals. IBD: Inflammatory bowel disease.

Table 3 Detection rates of Campylobacter concisus in fecal samples by two polymerase chain reaction methods

	Campylobacter genus PCR	Nested PCR
CD (n = 54)	19%	65%
Healthy controls (n = 33)	12%	33%
Non-IBD controls (n = 27)	0	37%

An example showing that different polymerase chain reaction (PCR) methods affect the detection of Campylobacter concisus (C. concisus) in intestinal samples. Data included in this table were from reference 18. Primers C412F and C1288R were used in campylobacter genus PCR. In nested PCR, PCR products amplified by primers C412F and C1288R were amplified again using C. concisus specific primers Concisus F and Concisus R. The nest PCR detected a significantly higher intestinal prevalence of C. concisus in patients with Crohn’s disease (CD) compared to both healthy controls and non-inflammatory bowel disease (IBD) controls. The genus PCR detected a significantly higher intestinal prevalence of C. concisus in patients with CD compared to non-IBD controls, but not healthy controls.

Table 4 Proteins encoded by putative prophages in Campylobacter concisus strain 13826

Nucleotide position	Locus tag	Encoded proteins	Size (aa)
1576686..1581986	CCC13826_0568	Hypothetical protein	1766
1582376..1583269	CCC13826_0638	Phage integrase	297
1583269..1583880	CCC13826_2272	Glutathionylspermidine synthase family	203
1583895..1585235	CCC13826_2273	Bacteriophage replication gene A protein	446
1585467..1585853	CCC13826_2274	Protein yitk	128
1585894..1586115	CCC13826_1101	Phosphonate uptake transporter	73
1586807..1587043	CCC13826_1102	Sensory box protein	78
1587044..1587496	CCC13826_2275	Hypothetical protein	150
1587598..1588506	CCC13826_2082	Phage integrase	302
1588755..1589966	CCC13826_1099	Putative phage replication protein A	403
1590015..1591184	CCC13826_1100	ATP binding protein (ABC) transporter	389
1591228..1592352	CCC13826_2276	Zonula occludens toxin (Zot) family protein	374
1592354..1592800	CCC13826_2277	Hypothetical protein	148
1592797..1594923	CCC13826_0183	Hypothetical protein	708
1594955..1595095	CCC13826_0184	Hypothetical protein	46
1595477..1595698	CCC13826_2278	Phosphonate uptake transporter	73
1596412..1596648	CCC13826_0164	Sensory box protein	78
1596649..1597101	CCC13826_2078	Hypothetical protein	150
1597203..1598111	CCC13826_2077	Phage integrase	302
1598360..1599571	CCC13826_0020	Putative phage replication protein A	403
1599620..1600789	CCC13826_0019	ABC transporter	389
1600833..1601957	CCC13826_2075	Zot family protein	374
1601959..1602405	CCC13826_2074	Hypothetical protein	148
1602402..1604528	CCC13826_1299	Hypothetical protein	708
1604560..1604700	CCC13826_1298	Hypothetical protein	46
1605082..1605303	CCC13826_2279	Phosphonate uptake transporter	73
1606017..1606253	CCC13826_0185	Sensory box protein	78
1606254..1606706	CCC13826_0186	Hypothetical protein	150
1606808..1607701	CCC13826_0706	Phage integrase	297
1607701..1608312	CCC13826_0188	Glutathionylspermidine synthase family	203
1608327..1609667	CCC13826_0189	Bacteriophage replication gene A protein	446
1609899..1611041	CCC13826_0190	Type II and III secretion system protein	380
1610992..1612116	CCC13826_0191	Hypothetical protein	374
1612118..1612438	CCC13826_0192	Hypothetical protein	106
1612537..1613946	CCC13826_0193	Hypothetical protein	469
1613956..1614075	CCC13826_0194	Alkyl hydroperoxide reductase	39
1614090..1614209	CCC13826_0195	Hypothetical protein	39
1614489..1614707	CCC13826_0196	Hypothetical protein	72
1614801..1615178	CCC13826_0197	Hypothetical protein	125

aa: Amino acids.

Table 5 The similarity of proteins in CON_phi3 and CON_phi4

CON_phi3	CON_phi4	Similarity1
CCC13826_0706	CCC13826_1213	23.23%
CCC13826_0188
CCC13826_0189	CCC13826_1212	93.72%
CCC13826_0190	CCC13826_1211	98.95%
CCC13826_0191	CCC13826_1210	92.25%
CCC13826_0192	CCC13826_1209	92.03%
CCC13826_0193	CCC13826_1208	58.90%
CCC13826_0194	CCC13826_2249	100%
CCC13826_0195	CCC13826_2248	97.44%
CCC13826_0196	CCC13826_1206	61.11%
CCC13826_0197	CCC13826_1205	95.24%

¹Similarity is the percentage of identical amino acids.

Table 6 Motifs shared by Campylobacter concisus zonula occludens toxin and zonulin/zonula occludens toxin receptor binding domains

C. concisus Zot1	GRF LSYHG
Human adult intestine zonulin	GGXL
Human fetal intestine zonulin	GGVLVQPG
C. concisus Zot2	GRF LSYHG
V. cholerae Zot	FCIGRLCVQDG

¹Campylobacter concisus zonula occludens toxin (Zot) and zonulin binding domain shares a motif (bold letters): Non-polar G, variable, non-polar, non-polar L, variable, polar, variable and non-polar G;

²C. concisus Zot and Vibrio cholerae Zot shares a motif (bold letters): non-polar G, basic polar R, non-polar, non-polar, variable, polar, variable and non-polar G. Comparison of C. concisus Zot and zonulin/Zot receptor was performed in this review. The amino acid sequences of human intestinal zonulin and V. cholerae Zot were obtained from reference 32.