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Sebastian Suerbaum

Publications and source records attributed to Sebastian Suerbaum.

30 records · Page 2Linked to original sources
PubMed2003

Helicobacter pylori flagellins have very low intrinsic activity to stimulate human gastric epithelial cells via TLR5.

Helicobacter pylori is a flagellated chronic pathogen, which colonizes the gastric mucus and mucosal cell surfaces. Flagella and motility are essential for the survival of this bacterium in the stomach environment. Flagellins of several bacterial species are potent activators of the human innate immune system by binding to TOLL-like receptor 5 (TLR5). The possible role of the two H. pylori flagellins FlaA and FlaB in stimulation of the innate immune system and induction of IL-8 release by human gastric epithelial cells was investigated in this study. Transcription and expression of TLR5 in three different human gastric epithelial cell lines was demonstrated. Salmonella enterica serovar Typhimurium FliC flagellin was able to activate human gastric epithelial cells. TLR5 transcription was modulated by H. pylori infection. However, both H. pylori flagellins appeared to possess no immunostimulatory potential on human gastric cells via TLR5, despite their extensive amino acid homology to stimulating flagellins of other bacterial species. The evolutionary development of such unique flagellins of low activating potential is proposed to be a novel mechanism of H. pylori to preserve the essential function of its flagella during chronic colonization of the stomach and to evade the deleterious host immune responses.

Cell Line↗
PubMed2003

Helicobacter pylori infection: CagA-specific antibodies are associated with clinical outcome, but not with HLA-class II polymorphisms of the host.

In order to investigate the interrelation between immunogenetic host and bacterial factors the T-cell receptor (TCR) polymorphism TCRBV6S1 A/B, HLA-DRB1 alleles and cagA status was analyzed in 380 unrelated German individuals. H. pylori infection with cagA-positive bacterial strains was significantly associated with peptic ulcer disease in the German cohort. Patients homozygous for the non-functional TCRBV6S1B allele and presenting with peptic ulcer disease showed no CagA-specific antibodies in the majority of cases. There was no association between HLA-DRB1 alleles and the CagA status of infected individuals, although certain alleles show significant association to the infection status in different populations.

Alleles↗
PubMed2003

Multilocus sequence analysis of Porphyromonas gingivalis indicates frequent recombination.

In this study, the genetic relationship of 19 Porphyromonas gingivalis isolates from patients with periodontitis was investigated by multilocus sequence analysis. Internal 400-600 bp DNA fragments of the 10 chromosomal genes ef-tu, ftsQ, hagB, gpdxJ, pepO, mcmA, dnaK, recA, pga and nah were amplified by PCR and sequenced. No two isolates were identical at all 10 loci. Phylogenetic analyses indicated a panmictic population structure of P. gingivalis. Split decomposition analysis, calculation of homoplasy ratios and analyses of clustered polymorphisms all indicate that recombination plays a major role in creating the genetic heterogeneity of P. gingivalis. A standardized index of association of 0.0898 indicates that the P. gingivalis genes analysed are close to linkage equilibrium.

Chromosomes, Bacterial↗
PubMed2002

The neuA/flmD gene cluster of Helicobacter pylori is involved in flagellar biosynthesis and flagellin glycosylation.

Helicobacter pylori possesses a gene (HP0326/JHP309) homologous to neuA of other bacteria, encoding a cytidyl monophosphate-N-acetylneuraminic acid synthetase-homologous enzyme in its N-terminal portion. We analysed the function of this gene, which is controlled by a flagellar class 2 sigma(54) promoter, in flagellar biosynthesis. HP0326/JHP309 actually represents a bicistronic operon consisting of a neuA and a flmD-like putative glycosyl transferase gene. An isogenic flmD mutant synthesized basal bodies but no filaments, was non-motile, and expressed severely reduced amounts of a FlaA flagellin of reduced molecular mass. FlaA flagellin was found to be glycosylated in its exported form within the flagellar filament, but not inside the cytoplasm. Glycosylated FlaA was not detectable in the flmD mutant. Together with other genes in the H. pylori genome, a proposed function of the neuA/flmD gene products could be to provide a pathway for glycosylation of flagellin and other extracytoplasmic molecules during type III secretion.

Blotting, Western↗
PubMed2002

Functional characterization of the antagonistic flagellar late regulators FliA and FlgM of Helicobacter pylori and their effects on the H. pylori transcriptome.

Helicobacter pylori is thought to regulate gene expression with a very small set of regulatory genes. We identified a previously unannotated open reading frame (ORF) in the H. pylori 26695 genome (HP1122) as a putative H. pylori flgM gene (sigma28 factor antagonist) by a motif-based bioinformatic approach. Deletion of HP1122 resulted in a fourfold increase in transcription of the sigma28-dependent major flagellin gene flaA, supporting the function of HP1122 as H. pylori FlgM. Helicobacter pylori FlgM lacks a conserved 20-amino-acid N-terminal domain of enterobacterial FlgM proteins, but was able to interact with the Salmonella typhimurium sigma28 (FliA) and inhibit the expression of FliA-dependent genes in Salmonella. Helicobacter pylori FlgM inhibited FliA to the same extent in a Salmonella strain with an intact flagellar export system and in an export-deficient strain. Helicobacter pylori FliA was able to drive transcription of FliA-dependent genes in Salmonella. The effects of mutations in the H. pylori flgM and fliA genes on the H. pylori transcriptome were analysed using whole genome DNA microarrays. The antagonistic roles of FlgM and FliA in controlling the transcription of the major flagellin gene flaA were confirmed, and two additional FliA/FlgM dependent operons (HP472 and HP1051/HP1052) were identified. None of the three genes contained in these operons has a known function in flagellar biogenesis in other bacteria. Like other motile bacteria, H. pylori has a FliA/FlgM pair of sigma and anti-sigma factors, but the genes controlled by these differ markedly from the Salmonella/Escherichia coli paradigm.

Amino Acid Sequence↗
PubMed2002

The role of motility as a virulence factor in bacteria.

Many bacteria that cause diseases of humans, animals and plants use flagella to move. This review summarises recent studies that have analysed the role of motility and chemotaxis in the host-parasite relationship of pathogenic bacteria. These studies have shown that for many pathogens, motility is essential in some phases of their life cycle and that virulence and motility are often intimately linked by complex regulatory networks. Possibilities to exploit bacterial motility as a specific therapeutic antibacterial target to cure or prevent disease are discussed.

Animals↗
PubMed2002

In the European population HLA-class II genes are not associated with Helicobacter pylori infection.

OBJECTIVE: Genetic variability influences susceptibility to several diseases and depends on the specific ethnic background of individuals. HLA-class II genes have repeatedly been investigated as candidate genes for predisposition to Helicobacter pylori infection. Certain HLA-DQA1 alleles have been reported to be associated with gastric and duodenal ulcer disease in infected patients in the Japanese population. But conflicting results were reported on European and Japanese populations. METHODS: HLA-DRB1 typing of 382 German individuals with well-defined H. pylori status and different clinical course of the disease was performed by polymerase chain reaction and allele-specific oligonucleotide hybridization. RESULTS: No association with the infection status itself was observed in the German cohort. Similar results have been found in other European populations. In contrast, re-analysis of published data in a Japanese cohort revealed a highly significant association of DRB1*1501 with uninfected controls (P = 0.00035). In the German population, the carrier frequency of DRB1*15 was higher in H. pylori-positive individuals with gastric or duodenal ulcer but without statistical significance (gastric ulcer: odds ratio, 2.13; chi2 = 3.77; P = 0.05; Bonferroni correction, Pc = not significant; and duodenal ulcer: odds ratio, 2.15; chi2 = 3.4; P = 0.06; Pc = not significant). In infected individuals, autoantibodies to gastric mucosa were investigated, but no statistical significant difference in carrier frequencies of HLA-DRB1 alleles was evident. CONCLUSION: The DRB1*1501-DQA1*01021-DQB1*0602 haplotype seems to provide protection from H. pylori infection in the Japanese population, whereas genetic variability in HLA-class II genes has only a minor impact on H. pylori infection and its clinical course in the European population.

Europe↗
PubMed2002

Helicobacter nemestrinae ATCC 49396T is a strain of Helicobacter pylori (Marshall et al. 1985) Goodwin et al. 1989, and Helicobacter nemestrinae Bronsdon et al. 1991 is therefore a junior heterotypic synonym of Helicobacter pylori.

Helicobacter nemestrinae Bronsdon et al. 1991, a gastric helicobacter species isolated from a pigtailed macaque, is thought to be the species most closely related to the important human pathogen Helicobacter pylori. The only available strain of this taxon is the type strain, ATCC 49396T. We sequenced seven housekeeping genes and two flagellin genes for H. nemestrinae ATCC 49396T. If ATCC 49396T were a separate species, these sequences should have been distinct from those of H. pylori. Instead, all sequences clustered together with sequences obtained previously for 20 or more H. pylori isolates from diverse geographical locations. The 16S rDNA sequence differed from that reported previously for this strain by 38 nucleotides and was most similar to that of H. pylori 85D08 (accession no. U00769), which was isolated from a rhesus macaque. It differed by less than 1% from 16S rDNA sequences of numerous other H. pylori strains, including the type strain, NCTC 11637T (= ATCC 43504T). These data indicate that the strain currently distributed as H. nemestrinae ATCC 49396T is really a strain of H. pylori and that H. nemestrinae Bronsdon et al. 1991 is a junior heterotypic synonym of Helicobacter pylori (Marshall et al. 1985) Goodwin et al. 1989.

Animals↗
PubMed2002

Growth phase-dependent and differential transcriptional control of flagellar genes in Helicobacter pylori.

Helicobacter pylori possesses two different flagellin genes, flaA and flaB, which are unlinked on the chromosome and transcribed from sigma(28) and sigma(54) promoters, respectively. Both flagellins are hypothesized to be present in varying amounts in the flagellum, to adapt the physical properties of the flagellar filament to different environmental conditions. The influence of growth phase and environmental conditions on the transcriptional regulation of both flagellin genes has not been investigated so far. Using three different reporter genes as well as Northern blot analyses and RT-PCR, it was determined that both flagellin genes are transcribed in a growth phase-dependent fashion. Growth phase dependency was also found for the flagellar basal body export apparatus gene flhA which is involved in the transcriptional regulation of both flagellin genes. Peak transcription of flaB and flhA occurred earlier during the growth phase than that of flaA, possibly consistent with a hook-proximal localization of the minor flagellin FlaB. Of the reporter gene systems, luciferase fusions reflected best the dynamic regulation patterns of H. pylori flagellin genes. Growth phase in vitro had the strongest influence on transcriptional control of H. pylori flaA and flaB, while differences in supplements to a rich culture medium had only a modest modulatory effect on flagellin gene transcription.

Bacterial Proteins↗
PubMedDate not supplied

Hepatic temporal gene expression profiling in Helicobacter hepaticus-infected A/JCr mice.

Helicobacter hepaticus infection of A/JCr mice is a model of infectious liver cancer. We monitored hepatic global gene expression profiles in H. hepaticus infected and control male A/JCr mice at 3 months, 6 months, and 1 year of age using an Affymetrix-based oligonucleotide microarray platform on the premise that a specific genetic expression signature at isolated time points would be indicative of disease status. Model based expression index comparisons generated by dChip yielded consistent profiles of differential gene expression for H. hepaticus infected male mice with progressive liver disease versus uninfected control mice within each age group. Linear discriminant analysis and principal component analysis allowed segregation of mice based on combined age and lesion status, or age alone. Up-regulation of putative tumor markers correlated with advancing hepatocellular dysplasia. Transcriptionally down-regulated genes in mice with liver lesions included those related to peroxisome proliferator, fatty acid, and steroid metabolism pathways. In conclusion, transcriptional profiling of hepatic genes documented gene expression signatures in the livers of H. hepaticus infected male A/JCr mice with chronic progressive hepatitis and preneoplastic liver lesions, complemented the histopathological diagnosis, and suggested molecular targets for the monitoring and intervention of disease progression prior to the onset of hepatocellular neoplasia.

Aging↗