Open Access

Genome sequence of Helicobacter suis supports its role in gastric pathology

  • Miet Vermoote1Email author,
  • Tom Theo Marie Vandekerckhove2,
  • Bram Flahou1,
  • Frank Pasmans1,
  • Annemieke Smet1,
  • Dominic De Groote3,
  • Wim Van Criekinge2,
  • Richard Ducatelle1 and
  • Freddy Haesebrouck1
Veterinary Research201142:51

DOI: 10.1186/1297-9716-42-51

Received: 10 December 2010

Accepted: 17 March 2011

Published: 17 March 2011

Abstract

Helicobacter (H.) suis has been associated with chronic gastritis and ulcers of the pars oesophagea in pigs, and with gastritis, peptic ulcer disease and gastric mucosa-associated lymphoid tissue lymphoma in humans. In order to obtain better insight into the genes involved in pathogenicity and in the specific adaptation to the gastric environment of H. suis, a genome analysis was performed of two H. suis strains isolated from the gastric mucosa of swine. Homologs of the vast majority of genes shown to be important for gastric colonization of the human pathogen H. pylori were detected in the H. suis genome. H. suis encodes several putative outer membrane proteins, of which two similar to the H. pylori adhesins HpaA and HorB. H. suis harbours an almost complete comB type IV secretion system and members of the type IV secretion system 3, but lacks most of the genes present in the cag pathogenicity island of H. pylori. Homologs of genes encoding the H. pylori neutrophil-activating protein and γ-glutamyl transpeptidase were identified in H. suis. H. suis also possesses several other presumptive virulence-associated genes, including homologs for mviN, the H. pylori flavodoxin gene, and a homolog of the H. pylori vacuolating cytotoxin A gene. It was concluded that although genes coding for some important virulence factors in H. pylori, such as the cytotoxin-associated protein (CagA), are not detected in the H. suis genome, homologs of other genes associated with colonization and virulence of H. pylori and other bacteria are present.

Introduction

Helicobacter (H.) suis is a very fastidious, spiral-shaped, Gram-negative bacterium requiring a biphasic culture medium at pH 5 enriched with fetal calf serum, and a microaerobic atmosphere for in vitro growth [1]. H. suis colonizes the stomach of more than 60% of slaughter pigs [1, 2]. Although the exact role of H. suis in gastric disease in pigs is still unclear, it has been associated with chronic gastritis [3, 4] and ulcers of the pars oesophagea of the stomach [57]. This may result in significant economic losses due to sudden death, decreased feed intake and reduced daily weight gain [8]. A reduction of approximately 20 g/day in weight gain was observed in animals experimentally infected with H. suis, compared to the non-infected control animals [9].

Bacterial gastric disorders in humans are mainly caused by Helicobacter pylori [10]. However, non-Helicobacter pylori helicobacters (NHPH) have also been associated with human gastric disease with a prevalence ranging between 0.2 and 6% [5]. H. suis is the most frequent NHPH species found in humans, where it was originally named "H. heilmannii" type 1 [11]. There are strong indications that pigs may serve as a source of infection for humans [5, 12]. In the human host, H. suis has been associated with peptic ulcer disease [13], gastric mucosa-associated lymphoid tissue (MALT) lymphoma [14] and chronic gastritis [15]. In rodent models of human gastric disease, the bacterium causes severe inflammation and MALT lymphoma-like lesions [16].

Up to now, little is known about the pathogenesis of H. suis infections. To improve understanding in the genes playing a role in pathogenicity, gastric colonization and persistence of H. suis, a genome-wide comparison with the well-investigated H. pylori genome was performed. Some virulence factors may indeed be similar for both bacteria. As there may also be differences, ab initio annotations of the H. suis genome were performed as well.

Materials and methods

Genome sequencing

A pyrosequencing (454 Life Sciences Corporation, Branford, CT, USA) assay was applied to the genome of the type strain of H. suis (HS1T = LMG 23995T = DSM 19735T) and H. suis strain 5 (HS5), isolated from the gastric mucosa of two different swine, according to the method described by Baele et al. [1]. Quality filtered sequences were assembled into contigs using a 454 Newbler assembler (Roche, Branford, CT, USA).

Functional annotation

In order to maximize the number of quality gene annotations, two different annotating approaches were followed: cross-mapping with three Helicobacter pylori strains (26695, Shi470, and G27 with NCBI accession numbers NC_000915, NC_010698, and NC_011333, respectively), and ab initio annotation.

Cross-mapping annotation

A custom BLAST [17] database was created from the HS1T and HS5 genomic contigs. The H. pylori proteome and non-coding RNAs were aligned (tblastn program of the BLAST suite, e threshold set to 10-3) to the H. suis database. For each BLAST hit the following additional information was analysed: 1) (secretion) signal peptide cleavage site if present, as assessed by the SignalP 3.0 program [18, 19]; 2) specifications of transmembrane helices (number, start and end positions, presumed topology with regard to the cytoplasmic membrane) if present, as assessed by the TMHMM program [20]; 3) an estimate of the ribosome binding strength of the mRNA region preceding the most probable start codon. Ribosome binding strength was estimated by applying two established facts: i) on an mRNA strand, usually within 20 nucleotides before the actual start codon, the reverse complement of 5 to 7 nucleotides near the 16S rRNA 3' end acts as an attractor and positioner for the ribosomal small subunit; this region is known as the Shine-Dalgarno sequence [21, 22]; ii) in Gram-negative bacteria an AU-rich mRNA region some 16 nucleotides long and immediately preceding the Shine-Dalgarno sequence may also attract and position ribosomes to help initiate translation of the correct, biologically active gene product [23, 24]. For H. suis, the Shine-Dalgarno sequence was determined to be a subsequence of AGGAGGU (which is the reverse complement of the 3' end of the 16S rRNA), and the minimum AU-richness (equivalent to ribosome binding capacity) of the preceding region was arbitrarily set to 10/16. For each theoretical ORF a range of possible start codons was scored; the higher the similarity to the ideal Shine-Dalgarno sequence, or the AU-richer the preceding region, or the better a combination of both, the more likely the potential start codon is to be the actual start codon.

Ab initio annotation

For ab initio annotation, theoretical open reading frames (ORFs) were first determined using the EMBOSS getorf tool (with minimum ORF length set to 90 nucleotides, and taking all alternative start codons into account) [25]. All ORFs were translated subsequently, and BLAST (blastp program) was performed with an e threshold of 10-15 against the Uniprot-KB universal protein database. The generalist algorithm of getorf yielded roughly a tenfold of the expected natural ORFs, reducing the risk of false negatives. In order to keep the false positive rate low, extra parameters were considered: 1) percentage alignment between query and hit ORFs; 2) percentage similarity or conservation between aligned portions of query and hit ORFs; 3) ribosome binding strength (for more details see above). To determine the presence of one or more conserved domains a rpsblast search (with default parameter values) was carried out for every single theoretical ORF against the compiled Conserved Domain Database which holds protein domain alignments from several other database sources [26].

Results

General features of the H. suis genome

In the HS1T genome a total of 1 635 292 base pairs and in the HS5 genome 1 669 960 bp were sequenced, both with an average GC content of 40%. In contrast to H. pylori, only one copy of both the 16S and 23S rRNA genes was detected, but like H. pylori, H. suis has three copies of the 5S rRNA gene. Thirty-eight transfer RNAs were identified. On the whole, 1266 ORFs from HS1T and 1257 from HS5 were detected, of which 194 and 191 encoded hypothetical proteins respectively. In 98 and 92 ORFs a signal peptide cleavage site was detected, demonstrating predicted secreted proteins of HS1T and HS5 respectively. The TMHMM program predicted 210 and 206 proteins with at least one transmembrane helix for HS1T and HS5 respectively. The sequence fraction identical for HS1T and HS5 is henceforward described together as the "H. suis genome".

Genes possibly involved in gastric colonization and persistence

Homologs of H. pylori genes involved in acid acclimation, chemotaxis, adhesion to gastric epithelial cells, oxidative stress resistance (Table 1), and motility were detected in the H. suis genome. The latter were identified as a flagellar biosystem similar to that of H. pylori [27]. Moreover, H. suis contains a fibrinonectin/fibrinogen-binding protein coding gene, but the corresponding protein lacks a transmembrane helix or signal peptide cleavage site according to the bioinformatics tools mentioned earlier. Homologs coding for CMP-N-acetylneuraminic acid synthetase (NeuA) (HSUHS1_0474, HSUHS5_0481), sialic acid synthase (NeuB) (HSUHS1_0477, HSUHS5_0478), and UDP-N-acetylglucosamine-2-epimerase (WecB) (HSUHS1_1107, HSUHS5_0784) were observed as well.
Table 1

Genes associated with pH homeostasis, chemotaxis, adhesion to epithelial cells, and oxidative stress resistance in the genome of H. suis type strain 1 (HS1T) and H. suis strain 5 (HS5).

Group

Gene detected in HS1T

Gene detected in HS5

Description of homolog

Percentage of sequence aligned (of which % conserved) with described homolog1

pH homeostasis

HSUHS1_0708

HSUHS5_0286

Urease subunit alfa (ureA) of H. heilmannii

100 (94)

 

HSUHS1_0707

HSUHS5_0285

Urease subunit beta (ureB) of H. heilmannii

100 (94)

 

HSUHS1_0706

HSUHS5_0284

Urease transporter (ureI) of H. felis

100 (89)

 

HSUHS1_0705

HSUHS5_0283

Urease accessory protein (ureE) of H. bizzozeronnii

100 (84)

 

HSUHS1_0704

HSUHS5_0282

Urease accessory protein (ureF) of H. bizzozeronnii

100 (84)

 

HSUHS1_0702

HSUHS5_0280

Urease accessory protein (ureH) of H. bizzozeronnii

96 (84)

 

HSUHS1_0703

HSUHS5_0281

Urease accessory protein (ureG) of H. bizzozeronnii

100 (95)

 

HSUHS1_0133

HSUHS5_0547

Hydrogenase expression/formation protein (hypA) of H. pylori

98 (83)

 

HSUHS1_0615

HSUHS5_0817

Hydrogenase expression/formation protein (hypB) of H. pylori

99 (91)

 

HSUHS1_0616

HSUHS5_0816

Hydrogenase expression/formation protein (hypC) of H. pylori

98 (89)

 

HSUHS1_0617

HSUHS5_0815

Hydrogenase expression/formation protein (hypD) of H. achinonychis

98 (80)

 

HSUHS1_0081

HSUHS5_1197

l-Asparaginase II (ansB) of H. pylori

98 (64)

 

HSUHS1_0230

HSUHS5_1130

Arginase (rocF) of H. pylori

99 (75)

 

HSUHS1_0888

HSUHS5_0231

Acylamide amidohydrolase (amiE) of H. pylori

100 (93)

 

HSUHS1_0680

HSUHS5_0265

Formamidase (amiF) of H. pylori

100 (98)

 

HSUHS1_0161

HSUHS5_1077

α-Carbonic anhydrase of H. pylori

92 (69)

 

HSUHS1_0391

HSUHS5_0874

Aspartase (aspA) of H. acinonychis

100 (89)

Chemotaxis

HSUHS1_1004

HSUHS5_0649

CheA-MCP interaction modulator of H. pylori

99 (79)

 

HSUHS1_1003

-

Bifunctional chemotaxis protein (cheF) of H. pylori

82 (86)

 

HSUHS1_1002

HSUHS5_0775

Purine-binding chemotaxis portein (cheW) of H. pylori

98 (91)

 

HSUHS1_0538

HSUHS5_0706

Chemotaxis protein (cheV) of H. pylori

100 (92)

 

HSUHS1_0846

HSUHS5_0081

Putative chemotaxis protein of H. pylori

100 (79)

 

HSUHS1_0299

HSUHS5_0250

Chemotaxis protein (cheY) of H. pylori

100 (95)

 

HSUHS1_1001

HSUHS5_0774

Methyl-accepting chemotaxis protein (tlpA) of H. pylori

100 (60)

 

HSUHS1_0286

HSUHS5_0256

Methyl-accepting chemotaxis protein ( tlpB) of H. pylori

98 (63)

 

HSUHS1_0479

HSUHS5_0476

Methyl- accepting chemotaxis protein of H. acinonychis

100 (66)

 

HSUHS1_0196

HSUHS5_0122

Methyl- accepting chemotaxis protein of Campylobacter upsaliensis 2

99 (53)

 

HSUHS1_0141

HSUHS5_0641

Methyl- accepting chemotaxis protein of Campylobacter fetus subsp. fetus 2

99 (64)

 

HSUHS1_0763

-

Methyl- accepting chemotaxis protein of Methylibium petroleiphilum 2

83 (52)

 

HSUHS1_0944

HSUHS5_0990

Methyl-accepting chemotaxis sensory transducer Marinomonas sp.2

57 (59)

Adhesion

HSUHS1_0666

HSUHS5_1053

Outer membrane protein (horB) of H. pylori

100 (63)

 

HSUHS1_0354

HSUHS5_0398

Neuraminyllactose-binding hemagglutinin (hpaA) of H. acinonychis

94 (77)

Oxidative stress resistance

HSUHS1_1147

HSUHS5_0608

Catalase (katA) of H. acinonychis

95 (82)

 

HSUHS1_0549

HSUHS5_1206

Mismatch repair ATPase (mutS) of H. hepaticus

99 (60)

 

HSUHS1_0163

HSUHS5_0495

Superoxide dismutase (sodB) of H. pylori

100 (90)

 

HSUHS1_1186

HSUHS5_0005

Bacterioferritin co-migratory protein of H. hepaticus

99 (72)

 

HSUHS1_0683

HSUHS5_0262

NAD(P)H quinone reductase (mdaB) of Campylobacter fetus subsp. fetus

97 (68)

 

HSUHS1_0689

HSUHS5_0268

Peroxiredoxin of H. pylori 3

100 (92)

1 Resulting from tblastn-based cross-mapping of the H. pylori proteome to the H. suis HS1T and HS5 genomes and blastp-based ab initio analyses of the translated H. suis HS1T and HS5 ORFs against the Uniprot-KB universal protein database. Differences between HS1T and HS5 homologs ≤ 1%.

2 Lacking in other Helicobacter genomes available at GenBank.

3 Member of the 2-Cys peroxiredoxin superfamily.

Genes encoding putative outer membrane proteins (OMPs) in relation to H. pylori OMPs are presented in Additional file 1 Table S1. Genes coding for members of major H. pylori OMP families (Hop, Hor, Hof proteins, iron-regulated and efflux pump OMPs) could be aligned with the H. pylori genome. Both H. suis strains contain the hof genes hofA, C, E, F, the hop genes hopE, G-2 and H, and the hor genes horB, C, D, and J. Additionally, HS1T contains homologs of the hopW protein precursor and horE, whereas HS5 possesses additional homologs of horA, horF, and horL. No members of the Helicobacter outer membrane (hom) family were detected in H. suis. Besides the major H. pylori OMP family proteins, the H. suis genome contains some predicted OMPs based on their N-terminal pattern of alternating hydrophobic amino acids similar to porins, encompassing omp29 for HS1T and omp11 and omp29 for HS5. A 491 amino acids membrane-associated homolog of the virulence factor MviN, aligned for 92% with the MviN homolog of H. acinonychis (Hac_1250), was also present in H. suis.

Type IV secretion systems in H. suis

Of the H. pylori type IV secretion systems (T4SS), only two members of the cag pathogenicity island (cag PAI) were identified in the H. suis genome (cag23/E and cagX). Most members of the comB transport apparatus were present. These include comB2, B3, B6, B8 and a number of additional genes not classified as comB: recA, comE, comL and dprA. H. suis possesses genes encoding VirB- and VirD-type ATPases (virB4, B8, B9, B10, B11, and virD2, D4), all designated members of the H. pylori type IV secretion system 3 (tfs3). The HS1T and HS5 T4SS are presented in Table 2.
Table 2

H. suis strain 1 (HS1T) and strain 5 (HS5) homologs of H. pylori and other Helicobacter sp. type IV secretion system genes.

Homolog

Gene detected in HS1T

Gene detected in HS5

Description of corresponding protein

Percentage of sequence fraction aligned (of which % conserved) with Helicobacter homolog1

cag pathogenicity island

    

   cag23/E of H. pylori

HSUHS1_0731

HSUHS5_1234

DNA transfer protein

81 (42)

   cagX of H. pylori

HSUHS1_0964

HSUHS5_0688

Conjugal plasmid transfer protein

92 (71)

comB system

    

   comB2 of H. acinonychis

HSUHS1_1181

HSUHS5_0010

ComB2 protein

96 (64)

   comB3 of H. acinonychis

HSUHS1_1182

HSUHS5_0009

ComB3 competence protein

95 (77)

   comB6 of H. pylori

HSUHS1_0337

-

NADH-ubiquinone oxidoreductase

70 (85)

   comB8 of H. pylori

HSUHS1_0747

Overlap with virB8

comB8 competence protein

93 (66)

   trbL of H. pylori

HSUHS1_0755

HSUHS5_0054

TrbL protein

99 (77)

   comE of H. acinonychis

HSUHS1_0314

HSUHS5_0381

Competence locus E

94 (55)

   comL of H. pylori

HSUHS1_0722

HSUHS5_0300

Competence protein

99 (84)

   dprA of H. acinonychis

HSUHS1_0096

HSUHS5_0824

DNA processing protein

99 (70)

   recA of H. hepaticus

HSUHS1_0672

HSUHS5_1058

Recombinase A

97 (84)

virB -homologs

    

   virB4 of H. pylori

HSUHS1_0960

HSUHS5_0692

DNA transfer protein

98 (68)

   virB8 of H. pylori

HSUHS1_0963

HSUHS5_0689

DNA transfer protein

91 (61)

   virB9 of H. cetorum

HSUHS1_0319

-

VirB9 protein

76 (69)

   virB10 of H. cetorum

HSUHS1_0320

-

VirB10 protein

90 (77)

   putative virB9 of H. pylori

-

HSUHS5_0372

Putative VirB9 protein

100 (86)

   putative virB10 of H. pylori

-

HSUHS5_0371

Putative VirB10 protein

97 (87)

   virB11 of H. pylori

HSUHS1_0750

HSUHS5_0368

VirB11 protein

100 (98)

   virB11 of H. cetorum

HSUHS1_0965

-

VirB11 protein

95 (71)

   virB11-like of H. pylori (HPSH_04565)

-

HSUHS5_0686

VirB11-like protein

98 (72)

   virB11-like of H. pylori (HPSH_07250)

HSUHS1_0036

HSUHS5_0600

Type IV ATPase

100 (75)

virD - homologs

    

   virD2 of H. cetorum

HSUHS1_0752

HSUHS5_0414

VirD2 protein (relaxase)

100 (90)

   virD4 of H.pylori

HSUHS1_0870

HSUHS5_0257

VirD4 protein (conjugation protein)

82 (78)

1 Resulting from tblastn-based cross-mapping of the H. pylori proteome to the H. suis HS1T and HS5 genomes and blastp-based ab initio analyses of the translated H. suis HS1T and HS5 ORFs against the Uniprot-KB universal protein database. Differences between HS1T and HS5 homologs ≤ 1%.

Genes possibly involved in induction of gastric lesions

Homologs of H. pylori genes involved in induction of gastric lesions in the H. suis genome are summarized in Table 3. Homology searches with the H. pylori vacuolating cytotoxin A gene (vacA) identified HSUHS1_0989 in HS1T. The corresponding protein, which is exceptional in that it is one of the longest in the world of prokaryotes, possesses three small conserved VacA regions (residues 490-545, 941-995, and 1043-1351), followed by an autotransporter region (residues 2730-2983). The amino acid sequence of the HS5 homolog (HSUHS5_0761) could be aligned for 22% with the H. pylori strain HPAG1 sequence, and possesses only one conserved VacA region (residues 242-298), followed by an autotransporter region (1258-1510). In both vacA homologs, no signal sequence was determined. Additionally, an ulcer-associated adenine-specific DNA methyltransferase (HSUHS1_0375, HSUHS5_0957) coding sequence was identified, whereas a molecular homolog of the ulcer-associated restriction endonuclease (iceA) could not be discovered in H. suis. H. suis contains homologs of pgbA and pgbB encoding plasminogen-binding proteins, though both lacking a transmembrane helix or signal peptide cleavage site according to the bioinformatics tools mentioned earlier. H. suis harbours homologs of genes coding for the H. pylori neutrophil-activating protein (HP-NapA) and γ-glutamyl transpeptidase (HP-GGT). Homologs encoding the H. pylori flavodoxin fldA and the pyruvate-oxidoreductase complex (POR) members porA, porB, porC, and porD were also identified in H. suis.
Table 3

Homologs of H. pylori genes involved in induction of gastric lesions in the H. suis type strain 1 (HS1T) and strain 5 (HS5) genome.

Gene detected in HS1T

Gene detected in HS5

Gene name

Protein annotation/function in H. pylori

Sequence fraction HS1T/HS5 aligned with H. pylori homolog (%)1

Aligned sequence fraction HS1T/HS5 conserved with H. pylori homolog (%)1

References

HSUHS1_0989

HSUHS5_0761

vacA

Vacuolating cytotoxin A: host cell vacuolation, apoptosis-inducing, immunosuppresive

63/22

45/72

[46]

HSUHS1_0265

HSUHS5_0449

ggt

γ-glutamyl transpeptidase: apoptosis-inducing, immunosuppresive

99/99

86/86

[48, 49, 64]

HSUHS1_1177

HSUHS5_0014

napA

Neutrophil-activating protein A: proinflammatory

99/99

83/83

[50, 51]

HSUHS1_1067

HSUHS5_1177

fldA

Electron acceptor of the pyruvate oxidoreductase enzyme complex, associated with gastric MALT lymphoma in humans

96/98

84/83

[55, 56]

HSUHS1_0403

HSUHS5_0887

pgbA

Plasminogen-binding protein

60/60

72/72

[53, 54]

HSUHS1_1192

HSUHS5_0523

pgbB

Plasminogen-binding protein

70/70

72/72

[53, 54]

1Resulting from tblastn-based cross-mapping of the H. pylori proteome to the H. suis HS1T and HS5 genomes.

Discussion

Genes possibly involved in gastric colonization and persistence

The results of the present study demonstrate that several H. pylori genes involved in acid acclimation, chemotaxis and motility, have counterparts in the H. suis genome. These genes are known to be essential for colonization of the human gastric mucosa [2732].

Several OMP coding sequences were identified by comparative analyses with H. pylori and other bacterial species. H. suis contains some similar members of the major OMP families described in H. pylori [33]. Some of these OMPs have been described to be involved in adhesion of H. pylori to the gastric mucosa, which is widely assumed to play an important role in the initial colonization and long-term persistence in the human stomach. These include the gastric epithelial cell adhesin HorB [34] and the surface lipoprotein, H. pylori adhesin A (HpaA). HpaA, also annotated as neuraminyllactose-binding hemagglutinin, is found exclusively in Helicobacter and binds to sialic acid-rich macromolecules present on the gastric epithelium [35]. On the other hand, H. suis lacks homologs of several other H. pylori adhesion factors, including genes coding for the blood group antigen binding adhesins babA (hopS) and babB (hopT), the sialic acid binding adhesins sabA (hopP) and sabB (hopO), and the adherence-associated lipoproteins alpA (hopC) and alpB (hopB) [36].

H. suis contains a fibrinonectin/fibrinogen-binding protein coding gene, which may enhance its adherence to injured gastric tissue. Damage to host epithelial cells may indeed expose fibronectin and other extracellular matrix components. Strong homology was found with fibronectin-binding proteins of H. felis (YP_004072974), H. canadensis (ZP_048703091) and Wolinella succinogenes (NP_907753). To our knowledge, no exact function has been given to these proteins in these species. In Campylobacter jejuni, however, fibronectin-binding proteins CadF and FlpA have been shown to be involved in adherence to and/or invasion of host's intestinal epithelial cells [37, 38]. According to the bioinformatics tools used here, the H. suis fibronectin-binding protein lacks a transmembrane helix or signal peptidase cleavage site, indicating that it is not surface exposed or secreted. Its real role in colonization therefore remains to be elucidated.

Three genes involved in sialic acid biosynthesis (neuA, neuB, and wecB) were annotated in the H. suis genome, indicating that this bacterium may decorate its surface with sialic acid. The presence of surface sialylation has been studied extensively in pathogenic bacteria, where it contributes to evasion of the host complement defense system [39].

Additionally, H. suis possesses genes encoding enzymes involved in oxidative-stress resistance (napA, sodB, katA, mutS, mdaB, and peroxiredoxin coding sequence). This indicates that H. suis may harbour a defense mechanism against the host inflammatory response, contributing to the ability of chronic gastric colonization by this bacterium [40].

Type IV secretion systems in H. suis

Two partial T4SS were predicted in the H. suis genome, namely the comB cluster and the tfs3 system. The H. suis comB system probably plays a role in genetic transformation [41, 42]. Transformation of DNA can be responsible for the high degree of diversity among H. suis strains as has been recently demonstrated by multilocus sequence typing of available H. suis strains [43]. The role of the H. pylori tfs3 secretion system in pathogenesis is not exactly known. Seven genes of the tfs3 cluster are homologs of genes involved in type IV secretion: virB4, virB11, and virD4 code for ATPases which move substrates to and through the pore. The latter is coded by transmembrane pore genes virB7, virB8, virB9, and virB10 [44]. All these genes, except virB7 were identified in H. suis, indicating that the H. suis tfs3 can be important in transmembrane transport of substrates in H. suis.

The H. pylori cag pathogenicity island (cag PAI) region encodes a T4SS allowing H. pylori to insert the cytotoxin-associated antigen A (CagA) into the host cell. This process results in altered host cell structure, an increased inflammatory response, and a higher risk for gastric adenocarcinoma [45]. Although H. suis possesses two members of the H. pylori cag PAI (cag23/E and cagX), the majority of genes, including the gene coding for pathology-causing protein (CagA), were not identified. This indicates that HS1T and HS5 lack a functional cag protein transporter secretion system.

Genes possibly involved in induction of gastric lesions

Genomic comparison of H. suis with H. pylori resulted in the identification of additional genes possibly associated with virulence in H. suis. A H. suis homolog of the H. pylori vacA was detected. VacA is both a cytotoxin of the gastric epithelial cell layer, and an immunomodulatory toxin of H. pylori [46]. H. pylori contains either a functional or non-functional vacA. The H. suis vacA homolog exhibits no vacA signal sequence, indicating that it might encode a non-functional cytotoxin [47]. In vitro and in vivo studies with a knockout mutant of the H. suis vacA could clarify the functionality of the vacA homolog in this Helicobacter species.

Strong homology was found with two H. pylori virulence-associated genes namely napA, encoding the HP-NapA and ggt, encoding HP-GGT. The H. pylori GGT has been identified as an apoptosis-inducing protein [48, 49]. The HP-NapA protein is designated as a proinflammatory and immunodominant protein by stimulating production of oxygen radicals and IL-12 from neutrophils and recruiting leukocytes in vivo [50, 51]. Moreover, HP-NapA also plays a role in protecting H. pylori from oxidative stress by binding free iron [52]. H. suis contains homologs of two H. pylori genes coding for plasminogen-binding proteins, pgbA and pgbB. The corresponding proteins, PgbA and PgbB bind host plasminogen, which subsequently can be activated to plasmin and may contribute to obstructing the natural healing process of gastric ulcers [53, 54]. The biological role of the H. suis pgbA and B homologs in chronicity of gastric ulceration is uncertain, as no exact membrane association was found in the corresponding proteins.

The risk to develop MALT lymphomas in H. suis infected human patients is higher than after infection with H. pylori [5, 14]. Homologs encoding the H. pylori flavodoxin (fldA) and its electron donor, the POR enzyme complex (porA to D) were found in H. suis. The H. pylori flavodoxin protein (FldA) has been proposed to play a role in the pathogenesis of H. pylori-associated MALT lymphoma, as antibodies against the H. pylori FldA protein were more prevalent in patients with MALT lymphomas compared to patients with other H. pylori- related diseases [55]. Besides, insertion mutagenesis of the fldA and the por complex has shown that these genes are essential for the survival of H. pylori [56]. These observations indicate that fldA and its por complex may play a role in gastric colonization of H. suis and MALT lymphoma development in H. suis infected people.

Recently, the genomes of the carcinogenic H. pylori strain B38 and the carcinogenic and ulcerogenic Helicobacter mustelae have been sequenced [57, 58]. Both helicobacters lack homologs of major H. pylori virulence genes (e.g. cagA, babA/B, sabA/B), which are also absent in the H. suis genome. Additionally, H. mustelae lacks a vacA homolog. Despite this absence, infection with H. pylori strain B38 and H. mustelae has been associated with gastric MALT lymphomas and other gastric disorders. Whole genome sequencing data are also available from H. acinonychis strain Sheeba, a gastric pathogen of large felines. Similar to H. suis, H. acinonychis lacks a cag PAI as well as genes encoding BabA/B and SabA/B. Both species contain a vacA homolog, which for H. acinonychis has been described to be fragmented [59, 60].

H. suis contains a mviN homolog. This gene has been described to be a virulence factor of several bacterial species, such as Burkholderia pseudomallei and Vibrio alginolyticus [61, 62]. In addition to virulence, MviN has been described to be essential for in vitro growth of these and other bacteria [6163]. The biological significance of mviN in the Helicobacter genus, however, remains to be elucidated.

Conclusion

Although H. suis lacks homologs of some major H. pylori virulence genes, other candidate virulence factors, such as napA, ggt, mviN, and fldA were detected. H. suis also possesses genes known to be essential for gastric colonization. Future in vitro and in vivo research of the currently presented genes of this porcine and human gastric pathogen should elucidate their precise role in colonization and virulence.

Nucleotide sequence accession numbers

The genome sequences have been deposited at GenBank/EMBL/DDBJ under the accession ADGY00000000 for HS1T and ADHO00000000 for HS5. The versions described in this paper are the first versions, ADGY1000000 and ADHO1000000.

Declarations

Acknowledgements

This work was supported by the Research Fund of Ghent University, Belgium (project no. 01G00408), and by the Agency for Innovation by Science and Technology in Flandres (IWT) (grant no. SB-091002). We thank Mrs Sofie De Bruyckere and Mrs Marleen Foubert for her technical support.

Authors’ Affiliations

(1)
Department of Pathology, Bacteriology and Avian Diseases, Faculty of Veterinary Medicine, Ghent University
(2)
Laboratory for Bioinformatics and Computational Genomics, Department of Molecular Biotechnology, Faculty of Bioscience Engineering, Ghent University
(3)
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Ghent University

References

  1. Baele M, Decostere A, Vandamme P, Ceelen L, Hellemans A, Chiers K, Ducatelle R, Haesebrouck F: Isolation and characterization of Helicobacter suis sp. nov. from pig stomachs. Int J Syst Evol Microbiol. 2008, 58: 1350-1358. 10.1099/ijs.0.65133-0.View ArticlePubMedGoogle Scholar
  2. Hellemans A, Chiers K, Maes D, De Bock M, Decostere A, Haesebrouck F, Ducatelle R: Prevalence of "Candidatus Helicobacter suis" in pigs of different ages. Vet Rec. 2007, 161: 182-192. 10.1136/vr.161.6.189.View ArticleGoogle Scholar
  3. Hellemans A, Chiers K, Decostere A, De Bock M, Haesebrouck F, Ducatelle R: Experimental infection of pigs with "Candidatus Helicobacter suis". Vet Res Commun. 2007, 31: 385-395. 10.1007/s11259-006-3448-4.View ArticlePubMedGoogle Scholar
  4. Mendes EN, Queiroz DM, Rocha GA, Nogueira AM, Carvalho AC, Lage AP, Barbosa AJ: Histopathological study of porcine gastric mucosa with and without a spiral bacterium ("Gastrospirillum suis"). J Med Microbiol. 1991, 35: 345-348. 10.1099/00222615-35-6-345.View ArticlePubMedGoogle Scholar
  5. Haesebrouck F, Pasmans F, Flahou B, Chiers K, Baele M, Meyns T, Decostere A, Ducatelle R: Gastric helicobacters in domestic animals and nonhuman primates and their significance for human health. Clin Microbiol. 2009, 22: 202-223. 10.1128/CMR.00041-08.View ArticleGoogle Scholar
  6. Queiroz DMM, Rocha GA, Mendes E, Moura SB, Rocha De Oliveira AM, Miranda D: Association between Helicobacter and gastric ulcer disease of the pars oesophagea in swine. Gastroenterology. 1996, 111: 19-27. 10.1053/gast.1996.v111.pm8698198.View ArticlePubMedGoogle Scholar
  7. Roosendaal R, Vos JH, Roumen T, Van Vugt R, Cattoli G, Bart A, Klaasen HL, Kuipers EJ, Vandenbroucke-Grauls CM, Kusters JG: Slaughter pigs are commonly infected with closely related but distinct gastric ulcerative lesion-inducing gastrospirilla. J Clin Microbiol. 2000, 38: 2661-2664.PubMed CentralPubMedGoogle Scholar
  8. Ayles HL, Friendship RM, Ball EO: Effect of dietary particle size on gastric ulcers, assessed by endoscopic examination, and relationship between ulcer severity and growth performance of individually fed pigs. Swine Health Prod. 1996, 4: 211-216.Google Scholar
  9. Kumar S, Chiers K, Pasmans F, Flahou B, Dewulf J, Haesebrouck F, Ducatelle R: An experimental Helicobacter suis infection reduces daily weight gain in pigs [abstract]. Helicobacter. 2010, 15: 324-Abstracts of the XXIIIrd International Workshop on Helicobacter and related bacteria in chronic digestive inflammation and gastric cancer 16-18/09/2010, Rotterdam, The NetherlandsGoogle Scholar
  10. Cover TL, Blaser MJ: Helicobacter pylori in health and disease. Gastroenterology. 2009, 136: 1863-1873. 10.1053/j.gastro.2009.01.073.PubMed CentralView ArticlePubMedGoogle Scholar
  11. O'Rourke JL, Solnick JV, Neilan BA, Seidel K, Hayter R, Hansen LM, Lee A: Description of "Candidatus Helicobacter heilmannii" based on DNA sequence analysis of 16S rRNA and urease genes. Int J Syst Evol Microbiol. 2004, 54: 2203-2211.View ArticlePubMedGoogle Scholar
  12. Meining A, Kroher G, Stolte M: Animal reservoirs in the transmission of Helicobacter heilmannii. Results of a questionnaire-based study. Scand J Gastroenterol. 1998, 33: 795-798. 10.1080/00365529850171422.View ArticlePubMedGoogle Scholar
  13. Debongnie JC, Donnay M, Mairesse J, Lamy V, Dekoninck X, Ramdani B: Gastric ulcers and Helicobacter heilmannii. Eur J Gastroenterol Hepatol. 1998, 10: 251-254. 10.1097/00042737-199803000-00011.View ArticlePubMedGoogle Scholar
  14. Morgner A, Bayerdorffer E, Meining A, Stolte M, Kroher G: Helicobacter heilmannii and gastric cancer. Lancet. 1995, 346: 551-552. 10.1016/S0140-6736(95)91364-5.View ArticleGoogle Scholar
  15. Debongnie JC, Donnay M, Mairesse J: Gastrospirillum hominis («Helicobacter heilmannii»): a cause of gastritis, sometimes transient, better diagnosed by touch cytology. Am J Gastroenterol. 1995, 90: 411-416.PubMedGoogle Scholar
  16. Flahou B, Haesebrouck F, Pasmans F, D'Herde K, Driessen A, Van Deun K, Smet A, Duchateau L, Chiers K, Ducatelle R: Helicobacter suis causes severe gastric pathology in mouse and Mongolian gerbil models of human gastric disease. 2010, PloS One, 5: e14083-Google Scholar
  17. Altschul SF, Madden TL, Schäffer AA, Zhang J, Zhang Z, Miller W, Lipman DJ: Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res. 1997, 25: 3389-3402. 10.1093/nar/25.17.3389.PubMed CentralView ArticlePubMedGoogle Scholar
  18. Bendtsen JD, Nielsen H, von Heijne G, Brunak S: Improved prediction of signal peptides: SignalP 3.0. J Mol Biol. 2004, 340: 783-795. 10.1016/j.jmb.2004.05.028.View ArticlePubMedGoogle Scholar
  19. Nielsen H, Engelbrecht J, Brunak S, von Heijne G: Identification of prokaryotic and eukaryotic signal peptides and prediction of their cleavage sites. Protein Eng. 1997, 10: 1-6. 10.1093/protein/10.1.1.View ArticlePubMedGoogle Scholar
  20. Krogh A, Larsson B, von Heijne G, Sonnhammer ELL: Predicting transmembrane protein topology with a hidden Markov model: application to complete genomes. J Mol Biol. 2001, 305: 567-580. 10.1006/jmbi.2000.4315.View ArticlePubMedGoogle Scholar
  21. Mikkonen M, Vuoristo J, Alatossava T: Ribosome binding site consensus sequence of Lactobacillus delbrueckii subsp. lactis bacteriophage LL-H. FEMS Microbiol Lett. 1994, 116: 315-320. 10.1111/j.1574-6968.1994.tb06721.x.View ArticlePubMedGoogle Scholar
  22. Shine J, Dalgarno L: The 3'-terminal sequence of E. coli 16S ribosomal RNA: complementarity to nonsense triplets and ribosome binding sites. Proc Natl Acad Sci USA. 1974, 71: 1342-1346. 10.1073/pnas.71.4.1342.PubMed CentralView ArticlePubMedGoogle Scholar
  23. Boni IV, Isaeva DM, Musychenko ML, Tzareva NV: Ribosome-messenger recognition: mRNA target sites for ribosomal protein S1. Nucleic Acids Res. 1991, 19: 155-162. 10.1093/nar/19.1.155.PubMed CentralView ArticlePubMedGoogle Scholar
  24. Komarova AV, Tchufistova LS, Dreyfus M, Boni IV: AU-rich sequences within 5' untranslated leaders enhance translation and stabilize mRNA in Escherichia coli. J Bacteriol. 2005, 187: 1344-1349. 10.1128/JB.187.4.1344-1349.2005.PubMed CentralView ArticlePubMedGoogle Scholar
  25. Rice P, Longden I, Bleasby A: EMBOSS: The European Molecular Biology Open Software Suite. Trends Genet. 2000, 16: 276-277. 10.1016/S0168-9525(00)02024-2.View ArticlePubMedGoogle Scholar
  26. Marchler-Bauer A, Anderson JB, Chitsaz F, Derbyshire MK, DeWeese-Scott C, Fong JH, Geer LY, Geer RC, Gonzales NR, Gwadz M, He S, Hurwitz DI, Jackson JD, Ke Z, Lanczycki CJ, Liebert CA, Liu C, Lu F, Lu S, Marchler GH, Mullokandov M, Song JS, Tasneem A, Thanki N, Yamashita RA, Zhang D, Zhang N, Bryant SH: CDD: specific functional annotation with the Conserved Domain Database. Nucleic Acids Res. 2009, 37: D205-D210. 10.1093/nar/gkn845.PubMed CentralView ArticlePubMedGoogle Scholar
  27. Tomb JF, White O, Kerlavage AR, Clayton RA, Sutton GG, Fleishmann RD, Ketchum KA, Klenk HP, Gill S, Dougherty BA, Nelson K, Quackenbush J, Zhou LX, Kirkness EF, Peterson S, Loftus B, Richardson D, Dodson R, Khalak HG, Glodek A, McKenney K, Fitzegerald LM, Lee N, Adams MD, Hickey EK, Berg DE, Gosayne JD, Utterback TR, Peterson JD, Kelley JM, Cotton MD, Weidman JM, Fujii C, Bowman C, Watthey L, Wallin E, Hayes WS, Borodovsky M, Karp PD, Smith HO, Fraser CM, Venter JC: The complete genome sequence of the gastric pathogen Helicobacter pylori. Nature. 1997, 388: 539-547. 10.1038/41483.View ArticlePubMedGoogle Scholar
  28. Eaton KA, Brooks CL, Morgan DR, Krakowka S: Essential role of urease in pathogenesis of gastritis inducted by Helicobacter pylori in gnotobiotic piglets. Infect Immun. 1991, 59: 2470-2475.PubMed CentralPubMedGoogle Scholar
  29. Kavermann H, Burns BP, Angermüller K, Odenbreit S, Fischer W, Melchers K, Haas R: Identification and characterization of Helicobacter pylori genes essential for gastric colonization. J Exp Med. 2003, 7: 813-822. 10.1084/jem.20021531.View ArticleGoogle Scholar
  30. Skouloubris S, Labigne A, De Reuse H: Identification and characterization of an aliphatic amidase in Helicobacter pylori. Mol Microbiol. 1997, 25: 989-998. 10.1111/j.1365-2958.1997.mmi536.x.View ArticlePubMedGoogle Scholar
  31. Skouloubris S, Labigne A, De Reuse H: The AmiE aliphatic amidase and AmiF formamidase of Helicobacter pylori: natural evolution of two enzyme paralogues. Mol Microbiol. 2001, 40: 596-609. 10.1046/j.1365-2958.2001.02400.x.View ArticlePubMedGoogle Scholar
  32. Wen Y, Marcus EA, Matrubutham U, Gleeson MA, Scott DR, Sachs G: Acid-adaptive genes of Helicobacter pylori. Infect Immun. 2003, 71: 5921-5939. 10.1128/IAI.71.10.5921-5939.2003.PubMed CentralView ArticlePubMedGoogle Scholar
  33. Alm RA, Bina J, Andrews BM, Doig P, Hancock REW, Trust TJ: Comparative genomics of Helicobacter pylori: analysis of the outer membrane protein families. Infect Immun. 2000, 68: 4155-4168. 10.1128/IAI.68.7.4155-4168.2000.PubMed CentralView ArticlePubMedGoogle Scholar
  34. Snelling WJ, Moran AP, Ryan KA, Scully P, McGourty K, Cooney JC, Annuk H, O'Toole PW: HorB (HP0127) is a gastric epithelial adhesion. Helicobacter. 2007, 12: 200-209. 10.1111/j.1523-5378.2007.00499.x.View ArticlePubMedGoogle Scholar
  35. Carlsohn E, Nyström J, Bolin I, Nilsson CL, Svennerholm AM: HpaA is essential for Helicobacter pylori colonization in mice. Infect Immun. 2006, 72: 920-926. 10.1128/IAI.74.2.920-926.2006.View ArticleGoogle Scholar
  36. Odenbreit S, Swoboda K, Barwig I, Ruhl S, Borén T, Koletzko S, Haas R: Outer membrane protein expression profile in Helicobacter pylori clinical isolates. Infect Immun. 2009, 77: 3782-3790. 10.1128/IAI.00364-09.PubMed CentralView ArticlePubMedGoogle Scholar
  37. Monteville MR, Yoon JE, Konkel ME: Maximal asherence and invasion of INT 407 cells by Campylobacter jejuni requires the CadF outer membrane protein and microfilament reorganization. Microbiology. 2003, 149: 153-165. 10.1099/mic.0.25820-0.View ArticlePubMedGoogle Scholar
  38. Konkel ME, Larson CL, Flanagan RC: Campylobacter jejuni FlpA binds fibronectin and is required for maximal host cell adherence. J Bacteriol. 2010, 192: 68-76. 10.1128/JB.00969-09.PubMed CentralView ArticlePubMedGoogle Scholar
  39. Severi E, Hood DW, Thomas GH: Sialic acid utilization by bacterial pathogens. Microbiology. 2007, 153: 2817-2822. 10.1099/mic.0.2007/009480-0.View ArticlePubMedGoogle Scholar
  40. Wang G, Alamuri P, Maier RJ: The diverse antioxidant systems of Helicobacter pylori. Mol Microbiol. 2006, 61: 847-860. 10.1111/j.1365-2958.2006.05302.x.View ArticlePubMedGoogle Scholar
  41. Hofreuter D, Odenbreit S, Haas R: Natural transformation competence in Helicobacter pylori is mediated by the basic competence of a type IV secretion system. Mol Microbiol. 2001, 41: 379-391. 10.1046/j.1365-2958.2001.02502.x.View ArticlePubMedGoogle Scholar
  42. Karnholz A, Hoefler C, Odenbreit S, Fischer W, Hofreuter D, Haas R: Functional and topological characterization of novel components of the comB DNA transformation competence system in Helicobacter pylori. J Bacteriol. 2006, 188: 882-893. 10.1128/JB.188.3.882-893.2006.PubMed CentralView ArticlePubMedGoogle Scholar
  43. Kumar S, Smet A, Flahou B, Vermoote M, Pasmans F, Chiers K, Ducatelle R, Haesebrouck F: Multilocus sequence typing (MLST) of Helicobacter suis [abstract]. Helicobacter. 2010, 15: 326-Abstracts of the XXIIIrd International Workshop on Helicobacter and related bacteria in chronic digestive inflammation and gastric cancer 16-18/09/2010, Rotterdam, The NetherlandsGoogle Scholar
  44. Kersulyte D, Velapatino B, Mukhopadhyay AK, Cahuayme L, Bussalleu A, Combe J, Gilman RH, Berg DE: Cluster of type IV secretion genes in Helicobacter pylori's plasticity zone. J Bacteriol. 2003, 185: 3764-3772. 10.1128/JB.185.13.3764-3772.2003.PubMed CentralView ArticlePubMedGoogle Scholar
  45. Backert S, Selbach M: Role of type IV secretion in Helicobacter pylori pathogenesis. Cell Microbiol. 2008, 10: 1573-1581. 10.1111/j.1462-5822.2008.01156.x.View ArticlePubMedGoogle Scholar
  46. Gebert B, Fischer W, Haas R: The Helicobacter pylori vacuolating cytotoxin: from cellular vacuolation to immunosuppressive activities. Rev Physiol Biochem Pharmacol. 2004, 152: 205-220. full_text.View ArticlePubMedGoogle Scholar
  47. Atherton JC, Cao P, Peek RM, Tummuru MKR, Blaser MJ, Cover TL: Mosaicism in vacuolating cytotoxin alleles of Helicobacter pylori. J Biol Chem. 1995, 270: 17771-17777. 10.1074/jbc.270.30.17771.View ArticlePubMedGoogle Scholar
  48. Kim KM, Lee SG, Park MG, Song JY, Kang HL, Lee WK, Cho MJ, Rhee KH, Joun HS, Baik SC: Gamma-glutamyltranspeptidase of Helicobacter pylori induces mitochondria-mediated apoptosis in AGS cells. Biochem Biophys Res Commun. 2007, 355: 562-567. 10.1016/j.bbrc.2007.02.021.View ArticlePubMedGoogle Scholar
  49. Shibayama K, Kamachi K, Nagata N, Yagi T, Nada T, Doi Y, Shibata N, Yokoyama K, Yamane K, Kato H, Iinuma Y, Arakawa Y: A novel apoptosis-inducing protein from Helicobacter pylori. Mol Microbiol. 2003, 47: 443-451. 10.1046/j.1365-2958.2003.03305.x.View ArticlePubMedGoogle Scholar
  50. Brisslert M, Enarsson K, Lundin S, Karlsson A, Kusters JG, Svennerholm S, Backert AM, Quiding-Järbrink M: Helicobacter pylori induce neutrophil transendothelial migration: role of the bacterial HP-NAP. FEMS Microbiol Lett. 2005, 249: 95-103. 10.1016/j.femsle.2005.06.008.View ArticlePubMedGoogle Scholar
  51. Wang CA, Liu YC, Dua SY, Lin CW, Fu HW: Helicobacter pylori neutrophil-activating protein promotes myeloperoxidase release from human neutrophils. Biochem Biophys Res Commun. 2008, 377: 52-56. 10.1016/j.bbrc.2008.09.072.View ArticlePubMedGoogle Scholar
  52. Cooksley C, Jenks PJ, Green A, Cockayne A, Logan RPH, Hardie KR: NapA protects Helicobacter pylori from oxidative stress damage, and its production is influenced by the ferric uptake regulator. J Med Microbiol. 2003, 52: 461-469. 10.1099/jmm.0.05070-0.View ArticlePubMedGoogle Scholar
  53. Jönsson K, Guo BP, Monstein HJ, Mekalanos JJ, Kronvall G: Molecular cloning and characterization of two Helicobacter pylori genes coding for plasminogen-binding proteins. Proc Natl Acad USA. 2004, 101: 1852-1857.View ArticleGoogle Scholar
  54. Ljung A: Helicobacter pylori interactions with plasminogen. Methods. 2000, 21: 151-157. 10.1006/meth.2000.0986.View ArticleGoogle Scholar
  55. Chang CS, Chen LT, Yang JC, Lin JT, Chang KC, Wang JT: Isolation of a Helicobacter pylori protein, FldA, associated with mucosa-associated lymphoid tissue lymphoma of the stomach. Gastroenterology. 1999, 117: 82-88. 10.1016/S0016-5085(99)70553-6.View ArticlePubMedGoogle Scholar
  56. Freigang J, Diederichs K, Schäfer KP, Welte W, Paul R: Crystal structure of oxidized flavodoxin, an essentiel protein in Helicobacter pylori. Protein Sci. 2001, 11: 253-261. 10.1110/ps.28602.View ArticleGoogle Scholar
  57. O'Toole PW, Snelling WJ, Canchaya C, Forde BM, Hardie KR, Josenhans C, Graham RLJ, McMullan G, Parkhill J, Belda E, Bentley SD: Comparative genomics and proteomics of Helicobacter mustelae, an ulcerogenic and carcinogenic pathogen. BMC Genomics. 2010, 11: 164-PubMed CentralView ArticlePubMedGoogle Scholar
  58. Thiberge JM, Boursaux-Eude C, Lehours P, Dillies MA, Creno S, Coppée JY, Rouy Z, Lajus A, Ma L, Burucoa C, Ruskoné-Foumestraux A, Courillon-Mallet A, De Reuse H, Boneca IG, Lamarque D, Mégraud F, Delchier JC, Médigue C, Bouchier C, Labigne A, Raymond J: Array-based hybridization of Helicobacter pylori isolates to the complete genome sequence of an isolate associated with MALT lymphoma. BMC Genomics. 2010, 11: 368-10.1186/1471-2164-11-368.PubMed CentralView ArticlePubMedGoogle Scholar
  59. Dailidiene D, Dailide G, Ogura K, Zhang M, Mukhopadhyay AK, Eaton KA, Cattoli G, Kusters JG, Berg DE: Helicobacter acinonychis: genetic and rodent infection studies of a Helicobacter pylori- like gastric pathogen of cheetahs and other big cats. J Bacteriol. 2004, 186: 356-365. 10.1128/JB.186.2.356-365.2004.PubMed CentralView ArticlePubMedGoogle Scholar
  60. Eppinger M, Baar C, Linz B, Raddatz G, Lanz C, Keller H, Morelli G, Gressmann H, Achtman M, Schuster ST: PloS Genet. 2006, 2: 1097-1110. 10.1371/journal.pgen.0020120.View ArticleGoogle Scholar
  61. Cao X, Wang Q, Liu Q, He H, Zhang Y: Vibrio alginolyticus MviN is a LuxO-regulated protein and affects cytotoxicity towards epithelioma paulosum cyprinid (EPC) cells. J Microbiol Biotechnol. 2010, 20: 271-280.View ArticlePubMedGoogle Scholar
  62. Ling JM, Moore RA, Surette MG, Woods DE: The mviN homolog in Burkholderia pseudomallei is essential for viability and virulence. Can J Microbiol. 2006, 52: 831-842. 10.1139/W06-042.View ArticlePubMedGoogle Scholar
  63. Inoue A, Murata Y, Takahashi H, Tsuji N, Fujisaki S, Kato JI: Involvement of an essential gene, mviN, in murein synthesis in Escherichia coli. J Bacteriol. 2008, 190: 7298-7301. 10.1128/JB.00551-08.PubMed CentralView ArticlePubMedGoogle Scholar
  64. Schmees C, Prinz C, Treptau T, Rad R, Hengst L, Voland P, Bauer S, Brenner L, Schmid RM, Gerhard M: Inhibition of T-cell proliferation by Helicobacter pylori γ-glutamyl transpeptidase. Gastroenterology. 2007, 132: 1820-1833. 10.1053/j.gastro.2007.02.031.View ArticlePubMedGoogle Scholar

Copyright

© Vermoote et al; licensee BioMed Central Ltd. 2011

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Advertisement