Sebastian Suerbaum

Publications

• 2.89

  Impact points

  The nucleotide excision repair (NER) system of Helicobacter pylori: Role in mutation prevention and chromosomal import patterns after natural transformation.

  Claudia Moccia, Juliane Krebes, Stefan Kulick, Xavier Didelot, Christian Kraft, Christelle Bahlawane, Sebastian Suerbaum

  BMC microbiology. 05/2012; 12(1):67.

  ABSTRACT: BACKGROUND: Extensive genetic diversity and rapid allelic diversification are characteristics of the human gastric pathogen Helicobacter pylori, and are believed to contribute to its ability to cause chronic infections. Both a high mutation rate and frequent imports of short fragments of e... [more] ABSTRACT: BACKGROUND: Extensive genetic diversity and rapid allelic diversification are characteristics of the human gastric pathogen Helicobacter pylori, and are believed to contribute to its ability to cause chronic infections. Both a high mutation rate and frequent imports of short fragments of exogenous DNA during mixed infections play important roles in generating this allelic diversity. In this study, we used a genetic approach to investigate the roles of nucleotide excision repair (NER) pathway components in H. pylori mutation and recombination. RESULTS: Inactivation of any of the four uvr genes strongly increased the susceptibility of H. pylori to DNA damage by ultraviolet light. Inactivation of uvrA and uvrB significantly decreased mutation frequencies whereas only the uvrA deficient mutant exhibited a significant decrease of the recombination frequency after natural transformation. A uvrC mutant did not show significant changes in mutation or recombination rates; however, inactivation of uvrC promoted the incorporation of significantly longer fragments of donor DNA (2.2-fold increase) into the recipient chromosome. A deletion of uvrD induced a hyper-recombinational phenotype. CONCLUSIONS: Our data suggest that the NER system has multiple functions in the genetic diversification of H. pylori, by contributing to its high mutation rate, and by controlling the incorporation of imported DNA fragments after natural transformation.
• 8.98

  Impact points

  Age of the Association between Helicobacter pylori and Man.

  Yoshan Moodley, Bodo Linz, Robert P Bond, Martin Nieuwoudt, Himla Soodyall, Carina M Schlebusch, Steffi Bernhöft, James Hale, Sebastian Suerbaum, Lawrence Mugisha, Schalk W van der Merwe, Mark Achtman

  PLoS pathogens. 05/2012; 8(5):e1002693.

  When modern humans left Africa ca. 60,000 years ago (60 kya), they were already infected with Helicobacter pylori, and these bacteria have subsequently diversified in parallel with their human hosts. But how long were humans infected by H. pylori prior to the out-of-Africa event? Did this co-evoluti... [more] When modern humans left Africa ca. 60,000 years ago (60 kya), they were already infected with Helicobacter pylori, and these bacteria have subsequently diversified in parallel with their human hosts. But how long were humans infected by H. pylori prior to the out-of-Africa event? Did this co-evolution predate the emergence of modern humans, spanning the species divide? To answer these questions, we investigated the diversity of H. pylori in Africa, where both humans and H. pylori originated. Three distinct H. pylori populations are native to Africa: hpNEAfrica in Afro-Asiatic and Nilo-Saharan speakers, hpAfrica1 in Niger-Congo speakers and hpAfrica2 in South Africa. Rather than representing a sustained co-evolution over millions of years, we find that the coalescent for all H. pylori plus its closest relative H. acinonychis dates to 88-116 kya. At that time the phylogeny split into two primary super-lineages, one of which is associated with the former hunter-gatherers in southern Africa known as the San. H. acinonychis, which infects large felines, resulted from a later host jump from the San, 43-56 kya. These dating estimates, together with striking phylogenetic and quantitative human-bacterial similarities show that H. pylori is approximately as old as are anatomically modern humans. They also suggest that H. pylori may have been acquired via a single host jump from an unknown, non-human host. We also find evidence for a second Out of Africa migration in the last 52,000 years, because hpEurope is a hybrid population between hpAsia2 and hpNEAfrica, the latter of which arose in northeast Africa 36-52 kya, after the Out of Africa migrations around 60 kya.
• 14.51

  Impact points

  Age, microbiota, and T cells shape diverse individual IgA repertoires in the intestine.

  Cornelia Lindner, Benjamin Wahl, Lisa Föhse, Sebastian Suerbaum, Andrew J Macpherson, Immo Prinz, Oliver Pabst

  The Journal of experimental medicine. 02/2012; 209(2):365-77.

  Intestinal immunoglobulin A (IgA) ensures host defense and symbiosis with our commensal microbiota. Yet previous studies hint at a surprisingly low diversity of intestinal IgA, and it is unknown to what extent the diverse Ig arsenal generated by somatic recombination and diversification is actually ... [more] Intestinal immunoglobulin A (IgA) ensures host defense and symbiosis with our commensal microbiota. Yet previous studies hint at a surprisingly low diversity of intestinal IgA, and it is unknown to what extent the diverse Ig arsenal generated by somatic recombination and diversification is actually used. In this study, we analyze more than one million mouse IgA sequences to describe the shaping of the intestinal IgA repertoire, its determinants, and stability over time. We show that expanded and infrequent clones combine to form highly diverse polyclonal IgA repertoires with very little overlap between individual mice. Selective homing allows expanded clones to evenly seed the small but not large intestine. Repertoire diversity increases during aging in a dual process. On the one hand, microbiota-, T cell-, and transcription factor RORγt-dependent but Peyer's patch-independent somatic mutations drive the diversification of expanded clones, and on the other hand, new clones are introduced into the repertoire of aged mice. An individual's IgA repertoire is stable and recalled after plasma cell depletion, which is indicative of functional memory. These data provide a conceptual framework to understand the dynamic changes in the IgA repertoires to match environmental and intrinsic stimuli.
• 3.76

  Impact points

  Closely related Campylobacter jejuni strains from different sources reveal a generalist rather than a specialist lifestyle.

  Eugenia Gripp, Daniela Hlahla, Xavier Didelot, Friederike Kops, Sven Maurischat, Karsten Tedin, Thomas Alter, Lüppo Ellerbroek, Kerstin Schreiber, Dietmar Schomburg, [......], Patrick Bartholomäus, Dirk Hofreuter, Sabrina Woltemate, Markus Uhr, Birgit Brenneke, Petra Grüning, Gerald Gerlach, Lothar Wieler, Sebastian Suerbaum, Christine Josenhans

  BMC genomics. 11/2011; 12:584.

  ABSTRACT: Campylobacter jejuni and Campylobacter coli are human intestinal pathogens of global importance. Zoonotic transmission from livestock animals or animal-derived food is the likely cause for most of these infections. However, little is known about their general and host-specific mechanisms o... [more] ABSTRACT: Campylobacter jejuni and Campylobacter coli are human intestinal pathogens of global importance. Zoonotic transmission from livestock animals or animal-derived food is the likely cause for most of these infections. However, little is known about their general and host-specific mechanisms of colonization, or virulence and pathogenicity factors. In certain hosts, Campylobacter species colonize persistently and do not cause disease, while they cause acute intestinal disease in humans. Here, we investigate putative host-specificity using phenotypic characterization and genome-wide analysis of genetically closely related C. jejuni strains from different sources. A collection of 473 fresh Campylobacter isolates from Germany was assembled between 2006 and 2010 and characterized using MLST. A subset of closely related C. jejuni strains of the highly prevalent sequence type ST-21 was selected from different hosts and isolation sources. PCR typing of strain-variable genes provided evidence that some genes differed between these strains. Furthermore, phenotypic variation of these strains was tested using the following criteria: metabolic variation, protein expression patterns, and eukaryotic cell interaction. The results demonstrated remarkable phenotypic diversity within the ST-21 group, which however did not correlate with isolation source. Whole genome sequencing was performed for five ST-21 strains from chicken, human, bovine, and food sources, in order to gain insight into ST-21 genome diversity. The comparisons showed extensive genomic diversity, primarily due to recombination and gain of phage-related genes. By contrast, no genomic features associated with isolation source or host were identified. The genome information and phenotypic data obtained in vitro and in a chicken infection model provided little evidence of fixed adaptation to a specific host. Instead, the dominant C. jejuni ST-21 appeared to be characterized by phenotypic flexibility and high genetic microdiversity, revealing properties of a generalist. High genetic flexibility might allow generalist variants of C. jejuni to reversibly express diverse fitness factors in changing environments.
• 5.18

  Impact points

  High TCR diversity ensures optimal function and homeostasis of Foxp3+ regulatory T cells.

  Lisa Föhse, Janine Suffner, Karsten Suhre, Benjamin Wahl, Cornelia Lindner, Chun-Wei Lee, Susanne Schmitz, Jan D Haas, Stella Lamprecht, Christian Koenecke, André Bleich, Günter J Hämmerling, Bernard Malissen, Sebastian Suerbaum, Reinhold Förster, Immo Prinz

  European journal of immunology. 09/2011; 41(11):3101-13.

  Dominant tolerance to self-antigen requires the presence of sufficient numbers of CD4(+) Foxp3(+) Treg cells with matching antigen specificity. However, the size and role of TCR repertoire diversity for antigen-specific immuno-regulation through Treg cells is not clear. Here, we developed and applie... [more] Dominant tolerance to self-antigen requires the presence of sufficient numbers of CD4(+) Foxp3(+) Treg cells with matching antigen specificity. However, the size and role of TCR repertoire diversity for antigen-specific immuno-regulation through Treg cells is not clear. Here, we developed and applied a novel high-throughput (HT) TCR sequencing approach to analyze the TCR repertoire of Treg cells and revealed the importance of high diversity for Treg-cell homeostasis and function. We found that highly polyclonal Treg cells from WT mice vigorously expanded after adoptive transfer into non-lymphopenic TCR-transgenic recipients with low Treg-cell diversity. In that system, we identified specific Treg-cell TCR preferences in distinct anatomic locations such as the mesenteric LN indicating that Treg cells continuously compete for MHC class-II-presented self-, food-, or flora-antigen. Functionally, we showed that high TCR diversity was required for optimal suppressive function of Treg cells in experimental acute graft versus host disease (GvHD). In conclusion, we suggest that efficient immuno-regulation by Treg cells requires high TCR diversity. Thereby, continuous competition of peripheral Treg cells for limited self-antigen shapes an organ-optimized, yet highly diverse, local TCR repertoire.
• 34.48

  Impact points

  No tech gaps in E. coli outbreak.

  Sebastian Suerbaum

  Nature. 08/2011; 476(7358):33.
• 9.43

  Impact points

  Helicobacter pylori genome evolution during human infection.

  Lynn Kennemann, Xavier Didelot, Toni Aebischer, Stefanie Kuhn, Bernd Drescher, Marcus Droege, Richard Reinhardt, Pelayo Correa, Thomas F Meyer, Christine Josenhans, Daniel Falush, Sebastian Suerbaum

  Proceedings of the National Academy of Sciences of the United States of America. 03/2011; 108(12):5033-8.

  High genetic diversity is a hallmark of the gastric pathogen Helicobacter pylori. We used 454 sequencing technology to perform whole-genome comparisons for five sets of H. pylori strains that had been sequentially cultured from four chronically infected Colombians (isolation intervals=3-16 y) and on... [more] High genetic diversity is a hallmark of the gastric pathogen Helicobacter pylori. We used 454 sequencing technology to perform whole-genome comparisons for five sets of H. pylori strains that had been sequentially cultured from four chronically infected Colombians (isolation intervals=3-16 y) and one human volunteer experimentally infected with H. pylori as part of a vaccine trial. The four sets of genomes from Colombian H. pylori differed by 27-232 isolated SNPs and 16-441 imported clusters of polymorphisms resulting from recombination. Imports (mean length=394 bp) were distributed nonrandomly over the chromosome and frequently occurred in groups, suggesting that H. pylori first takes up long DNA fragments, which subsequently become partially integrated in multiple shorter pieces. Imports were present at significantly increased frequency in members of the hop family of outer membrane gene paralogues, some of which are involved in bacterial adhesion, suggesting diversifying selection. No evidence of recombination and few other differences were identified in the strain pair from an infected volunteer, indicating that the H. pylori genome is stable in the absence of mixed infection. Among these few differences was an OFF/ON switch in the phase-variable adhesin gene hopZ, suggesting strong in vivo selection for this putative adhesin during early colonization.
• 0.50

  Impact points

  [Frequency of polyphasic health-care-associated outbreaks is highest in surgical departments - results of a systematic literature search].

  S Thon, K Graf, S Suerbaum, R-P Vonberg

  Zentralblatt für Chirurgie. 02/2011; 136(1):74-8.

  So-called polyphasic nosocomial outbreaks describe a situation in which additional infections occur after a certain case-free interval - despite the detection of the outbreak's source. This article summarises the results of a systematic search of the medical literature on polyphasic outbreaks. F... [more] So-called polyphasic nosocomial outbreaks describe a situation in which additional infections occur after a certain case-free interval - despite the detection of the outbreak's source. This article summarises the results of a systematic search of the medical literature on polyphasic outbreaks. For this purpose, the Outbreak Worldwide-Database, PubMed and reference lists of relevant articles were screened. A total of 124 polyphasic outbreaks (median duration of 50 weeks) was included in the analysis and then compared to 2089 monophasic nosocomial outbreaks. Surgical departments were significantly more often involved in polyphasic outbreaks than they were in monophasic events (33.9 % vs. 24.5 %; p < 0.05). Hepatitis B virus outbreaks were significantly more often seen as poly-phasic events. Either there had been more than one source initially, or a new source developed during the first phase of the outbreak and led to additional cases thereafter. Up to now, only little is known about polyphasic nosocomial outbreaks. Thus, there is a further need to close this gap of information in the future. Personnel on the ward as well as -infection control staff should always consider the possibility of the existence of more than one -source when investigating a nosocomial outbreak.
• 2.72

  Impact points

  Systematic cross-validation of 454 sequencing and pyrosequencing for the exact quantification of DNA methylation patterns with single CpG resolution.

  Anna Potapova, Cord Albat, Britta Hasemeier, Katrin Haeussler, Stella Lamprecht, Sebastian Suerbaum, Hans Kreipe, Ulrich Lehmann

  BMC biotechnology. 01/2011; 11:6.

  New high-throughput sequencing technologies promise a very sensitive and high-resolution analysis of DNA methylation patterns in quantitative terms. However, a detailed and comprehensive comparison with existing validated DNA methylation analysis methods is not yet available. Therefore, a systematic... [more] New high-throughput sequencing technologies promise a very sensitive and high-resolution analysis of DNA methylation patterns in quantitative terms. However, a detailed and comprehensive comparison with existing validated DNA methylation analysis methods is not yet available. Therefore, a systematic cross-validation of 454 sequencing and conventional pyrosequencing, both of which offer exact quantification of methylation levels with a single CpG dinucleotide resolution, was performed. To this end the methylation patterns of 12 loci (GSTπ1, p16INK4a, RASSF1A, SOCS1, MAL, hsa-mir-1-1, hsa-mir-9-3, hsa-mir-34a, hsa-mir-596, hsa-mir-663, MINT31, and LINE-1) were analyzed in ten primary hepatocellular carcinoma specimens. After applying stringent quality control criteria, 35749 sequences entered further analysis. The methylation level of individual CpG dinucleotides obtained by 454 sequencing was systematically compared with the corresponding values obtained by conventional pyrosequencing. Statistical analyses revealed an excellent concordance of methylation levels for all individual CpG dinucleotides under study (r2 = 0.927). Our results confirm that 454 sequencing of bisulfite treated genomic DNA provides reliable high quality quantitative methylation data and identify MAL, hsa-mir-9-3, hsa-mir-596, and hsa-mir-663 as new targets of aberrant DNA methylation in human hepatocellular carcinoma. In addition, the single molecule resolution of 454 sequencing provides unprecedented information about the details of DNA methylation pattern heterogeneity in clinical samples.
• 3.94

  Impact points

  Molecular evolution of the Helicobacter pylori vacuolating toxin gene vacA.

  Kelly A Gangwer, Carrie L Shaffer, Sebastian Suerbaum, D Borden Lacy, Timothy L Cover, Seth R Bordenstein

  Journal of bacteriology. 12/2010; 192(23):6126-35.

  Helicobacter pylori is a genetically diverse organism that is adapted for colonization of the human stomach. All strains contain a gene encoding a secreted, pore-forming toxin known as VacA. Genetic variation at this locus could be under strong selection as H. pylori adapts to the host immune respon... [more] Helicobacter pylori is a genetically diverse organism that is adapted for colonization of the human stomach. All strains contain a gene encoding a secreted, pore-forming toxin known as VacA. Genetic variation at this locus could be under strong selection as H. pylori adapts to the host immune response, colonizes new human hosts, or inhabits different host environments. Here, we analyze the molecular evolution of VacA. Phylogenetic reconstructions indicate the subdivision of VacA sequences into three main groups with distinct geographic distributions. Divergence of the three groups is principally due to positively selected sequence changes in the p55 domain, a central region required for binding of the toxin to host cells. Divergent amino acids map to surface-exposed sites in the p55 crystal structure. Comparative phylogenetic analyses of vacA sequences and housekeeping gene sequences indicate that vacA does not share the same evolutionary history as the core genome. Further, rooting the VacA tree with outgroup sequences from the close relative Helicobacter acinonychis reveals that the ancestry of VacA is different from the African origin that typifies the core genome. Finally, sequence analyses of the virulence determinant CagA reveal three main groups strikingly similar to the three groups of VacA sequences. Taken together, these results indicate that positive selection has shaped the phylogenetic structure of VacA and CagA, and each of these virulence determinants has evolved separately from the core genome.
• 12.90

  Impact points

  Lack of commensal flora in Helicobacter pylori-infected INS-GAS mice reduces gastritis and delays intraepithelial neoplasia.

  Jennifer L Lofgren, Mark T Whary, Zhongming Ge, Sureshkumar Muthupalani, Nancy S Taylor, Melissa Mobley, Amanda Potter, Andrea Varro, Daniel Eibach, Sebastian Suerbaum, Timothy C Wang, James G Fox

  Gastroenterology. 10/2010; 140(1):210-20.

  Transgenic FVB/N insulin-gastrin (INS-GAS) mice have high circulating gastrin levels, and develop spontaneous atrophic gastritis and gastrointestinal intraepithelial neoplasia (GIN) with 80% prevalence 6 months after Helicobacter pylori infection. GIN is associated with gastric atrophy and achlorhyd... [more] Transgenic FVB/N insulin-gastrin (INS-GAS) mice have high circulating gastrin levels, and develop spontaneous atrophic gastritis and gastrointestinal intraepithelial neoplasia (GIN) with 80% prevalence 6 months after Helicobacter pylori infection. GIN is associated with gastric atrophy and achlorhydria, predisposing mice to nonhelicobacter microbiota overgrowth. We determined if germfree INS-GAS mice spontaneously develop GIN and if H pylori accelerates GIN in gnotobiotic INS-GAS mice. We compared gastric lesions, levels of messenger RNA, serum inflammatory mediators, antibodies, and gastrin among germfree and H pylori-monoinfected INS-GAS mice. Microbiota composition of specific pathogen-free (SPF) INS-GAS mice was quantified by pyrosequencing. Germfree INS-GAS mice had mild hypergastrinemia but did not develop significant gastric lesions until 9 months old and did not develop GIN through 13 months. H pylori monoassociation caused progressive gastritis, epithelial defects, oxyntic atrophy, marked foveolar hyperplasia, dysplasia, and robust serum and tissue proinflammatory immune responses (particularly males) between 5 and 11 months postinfection (P<0.05, compared with germfree controls). Only 2 of 26 female, whereas 8 of 18 male, H pylori-infected INS-GAS mice developed low to high-grade GIN by 11 months postinfection. Stomachs of H pylori-infected SPF male mice had significant reductions in Bacteroidetes and significant increases in Firmicutes. Gastric lesions take 13 months longer to develop in germfree INS-GAS mice than male SPF INS-GAS mice. H pylori monoassociation accelerated gastritis and GIN but caused less severe gastric lesions and delayed onset of GIN compared with H pylori-infected INS-GAS mice with complex gastric microbiota. Changes in gastric microbiota composition might promote GIN in achlorhydric stomachs of SPF mice.
• 17.64

  Impact points

  The impact of the microbiota on the pathogenesis of IBD: lessons from mouse infection models.

  Sandra Nell, Sebastian Suerbaum, Christine Josenhans

  Nature reviews. Microbiology. 08/2010; 8(8):564-77.

  Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, is a major human health problem. The bacteria that live in the gut play an important part in the pathogenesis of IBD. However, owing to the complexity of the gut microbiota, our understanding of the roles of comm... [more] Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, is a major human health problem. The bacteria that live in the gut play an important part in the pathogenesis of IBD. However, owing to the complexity of the gut microbiota, our understanding of the roles of commensal and pathogenic bacteria in establishing a healthy intestinal barrier and in its disruption is evolving only slowly. In recent years, mouse models of intestinal inflammatory disorders based on defined bacterial infections have been used intensively to dissect the roles of individual bacterial species and specific bacterial components in the pathogenesis of IBD. In this Review, we focus on the impact of pathogenic and commensal bacteria on IBD-like pathogenesis in mouse infection models and summarize important recent developments.
• 6.71

  Impact points

  Routine bile collection for microbiological analysis during cholangiography and its impact on the management of cholangitis.

  Ahmed A Negm, Anja Schott, Ralf-Peter Vonberg, Tobias J Weismueller, Andrea S Schneider, Stefan Kubicka, Christian P Strassburg, Michael P Manns, Sebastian Suerbaum, Jochen Wedemeyer, Tim O Lankisch

  Gastrointestinal endoscopy. 08/2010; 72(2):284-91.

  Antibiotic treatment of cholangitis is often insufficient because of inappropriate antibiotic use or bacterial resistance. To evaluate the role of routine bile collection during endoscopic retrograde cholangiography or percutaneous transhepatic cholangiography for microbiological analysis in the ant... [more] Antibiotic treatment of cholangitis is often insufficient because of inappropriate antibiotic use or bacterial resistance. To evaluate the role of routine bile collection during endoscopic retrograde cholangiography or percutaneous transhepatic cholangiography for microbiological analysis in the antibiotic management of cholangitis and to identify risk factors of bacteriobilia. Prospective, observational, diagnostic study. Hannover Medical School, Hannover, Germany. This study involved 243 consecutive patients undergoing endoscopic retrograde cholangiography/percutaneous transhepatic cholangiography for biliary complications after orthotopic liver transplantation (27%), malignancy (27%), primary sclerosing cholangitis (15%), benign strictures (11%), and choledocholithiasis (8%). Microbiological examination of bile samples. Patients with biliary stents or who were receiving repeated interventions after orthotopic liver transplantation were at increased risk of bacteriobilia (P < .05). The rate of gram-positive monomicrobial infection was higher in patients with primary sclerosing cholangitis (P < .01). In 40 examinations, patients presented with preprocedural cholangitis although they were receiving antibiotics. According to bile culture results, the antibiotic treatment was modified to a more specific therapy in 72.5% of patients. In patients who developed cholangitis after endoscopic retrograde cholangiography (27 examinations), specific antibiotic treatment was started or refined in 67% of cases, based on bile culture results. Contamination of samples during intervention cannot be totally excluded. Orthotopic liver transplantation, biliary stenting, and repeated interventions are risk factors of bacteriobilia. In our patients with primary sclerosing cholangitis, gram-positive monomicrobial infections were more common. A bile sample collected during cholangiography for microbiological analysis is a simple, potentially valuable, diagnostic tool in patients with cholangitis. Each center should recognize its own patterns of infection to ensure ideal targeted therapy.
• 9.53

  Impact points

  A global overview of the genetic and functional diversity in the Helicobacter pylori cag pathogenicity island.

  Patrick Olbermann, Christine Josenhans, Yoshan Moodley, Markus Uhr, Christiana Stamer, Marc Vauterin, Sebastian Suerbaum, Mark Achtman, Bodo Linz

  PLoS genetics. 08/2010; 6(8):e1001069.

  The Helicobacter pylori cag pathogenicity island (cagPAI) encodes a type IV secretion system. Humans infected with cagPAI-carrying H. pylori are at increased risk for sequelae such as gastric cancer. Housekeeping genes in H. pylori show considerable genetic diversity; but the diversity of virulence ... [more] The Helicobacter pylori cag pathogenicity island (cagPAI) encodes a type IV secretion system. Humans infected with cagPAI-carrying H. pylori are at increased risk for sequelae such as gastric cancer. Housekeeping genes in H. pylori show considerable genetic diversity; but the diversity of virulence factors such as the cagPAI, which transports the bacterial oncogene CagA into host cells, has not been systematically investigated. Here we compared the complete cagPAI sequences for 38 representative isolates from all known H. pylori biogeographic populations. Their gene content and gene order were highly conserved. The phylogeny of most cagPAI genes was similar to that of housekeeping genes, indicating that the cagPAI was probably acquired only once by H. pylori, and its genetic diversity reflects the isolation by distance that has shaped this bacterial species since modern humans migrated out of Africa. Most isolates induced IL-8 release in gastric epithelial cells, indicating that the function of the Cag secretion system has been conserved despite some genetic rearrangements. More than one third of cagPAI genes, in particular those encoding cell-surface exposed proteins, showed signatures of diversifying (Darwinian) selection at more than 5% of codons. Several unknown gene products predicted to be under Darwinian selection are also likely to be secreted proteins (e.g. HP0522, HP0535). One of these, HP0535, is predicted to code for either a new secreted candidate effector protein or a protein which interacts with CagA because it contains two genetic lineages, similar to cagA. Our study provides a resource that can guide future research on the biological roles and host interactions of cagPAI proteins, including several whose function is still unknown.
• 9.53

  Impact points

  Microevolution of Helicobacter pylori during prolonged infection of single hosts and within families.

  Giovanna Morelli, Xavier Didelot, Barica Kusecek, Sandra Schwarz, Christelle Bahlawane, Daniel Falush, Sebastian Suerbaum, Mark Achtman

  PLoS genetics. 07/2010; 6(7):e1001036.

  Our understanding of basic evolutionary processes in bacteria is still very limited. For example, multiple recent dating estimates are based on a universal inter-species molecular clock rate, but that rate was calibrated using estimates of geological dates that are no longer accepted. We therefore e... [more] Our understanding of basic evolutionary processes in bacteria is still very limited. For example, multiple recent dating estimates are based on a universal inter-species molecular clock rate, but that rate was calibrated using estimates of geological dates that are no longer accepted. We therefore estimated the short-term rates of mutation and recombination in Helicobacter pylori by sequencing an average of 39,300 bp in 78 gene fragments from 97 isolates. These isolates included 34 pairs of sequential samples, which were sampled at intervals of 0.25 to 10.2 years. They also included single isolates from 29 individuals (average age: 45 years) from 10 families. The accumulation of sequence diversity increased with time of separation in a clock-like manner in the sequential isolates. We used Approximate Bayesian Computation to estimate the rates of mutation, recombination, mean length of recombination tracts, and average diversity in those tracts. The estimates indicate that the short-term mutation rate is 1.4 x 10(-6) (serial isolates) to 4.5 x 10(-6) (family isolates) per nucleotide per year and that three times as many substitutions are introduced by recombination as by mutation. The long-term mutation rate over millennia is 5-17-fold lower, partly due to the removal of non-synonymous mutations due to purifying selection. Comparisons with the recent literature show that short-term mutation rates vary dramatically in different bacterial species and can span a range of several orders of magnitude.
• 4.41

  Impact points

  Ethnic and geographic differentiation of Helicobacter pylori within Iran.

  Saeid Latifi-Navid, Seyed Ali Ghorashi, Farideh Siavoshi, Bodo Linz, Sadegh Massarrat, Tanya Khegay, Ali-Hatef Salmanian, Ali Akbar Shayesteh, Mohsen Masoodi, Koroush Ghanadi, Azita Ganji, Sebastian Suerbaum, Mark Achtman, Reza Malekzadeh, Daniel Falush

  PloS one. 01/2010; 5(3):e9645.

  The bacterium Helicobacter pylori colonizes the human stomach, with individual infections persisting for decades. The spread of the bacterium has been shown to reflect both ancient and recent human migrations. We have sequenced housekeeping genes from H. pylori isolated from 147 Iranians with well-c... [more] The bacterium Helicobacter pylori colonizes the human stomach, with individual infections persisting for decades. The spread of the bacterium has been shown to reflect both ancient and recent human migrations. We have sequenced housekeeping genes from H. pylori isolated from 147 Iranians with well-characterized geographical and ethnic origins sampled throughout Iran and compared them with sequences from strains from other locations. H. pylori from Iran are similar to others isolated from Western Eurasia and can be placed in the previously described HpEurope population. Despite the location of Iran at the crossroads of Eurasia, we found no evidence that the region been a major source of ancestry for strains across the continent. On a smaller scale, we found genetic affinities between the H. pylori isolated from particular Iranian populations and strains from Turks, Uzbeks, Palestinians and Israelis, reflecting documented historical contacts over the past two thousand years.
• 4.64

  Impact points

  Role of the C5a receptor (C5aR) in acute and chronic dextran sulfate-induced models of inflammatory bowel disease.

  Kay Johswich, Myriam Martin, André Bleich, Michael Kracht, Oliver Dittrich-Breiholz, J Engelbert Gessner, Sebastian Suerbaum, Elisabeth Wende, Claudia Rheinheimer, Andreas Klos

  Inflammatory bowel diseases. 09/2009;

  BACKGROUND:: Inflammatory bowel disease (IBD) is a critical public health issue; more and more people are affected, but treatment options remain limited. Complement activation and the anaphylatoxin C5a have been shown to play a role in IBD. In this study, mouse models of acute and chronic dextran su... [more] BACKGROUND:: Inflammatory bowel disease (IBD) is a critical public health issue; more and more people are affected, but treatment options remain limited. Complement activation and the anaphylatoxin C5a have been shown to play a role in IBD. In this study, mouse models of acute and chronic dextran sulfate-induced colitis were used to further elucidate the impact of C5a and its receptor (C5aR) on disease development. METHODS:: In C57BL/6J wildtype and C5aR(-/-) mice the extent of complement activation, changes in weight, and water/food consumption were determined. Disease severity was evaluated via a clinical score, histology, cytokine- and myeloperoxidase-determination as well as real-time reverse-transcriptase polymerase chain reaction (RT-PCR) for expression of anaphylatoxin receptors and inflammatory mediators. RESULTS:: C5aR(-/-) mice showed milder disease symptoms, less histological damage, and a lower expression of inflammatory mediators in acute colitis, a setting where complement was activated. In chronic colitis the knockout mice exhibited aggravated weight loss, a higher degree of histological damage and granulocyte infiltration. Intriguingly, increases in C3a-receptor and C5L2 mRNA were dependent on C5aR. Compared to wildtype mice, C5aR(-/-) animals displayed smaller lymph nodes in acute colitis, but extensive swelling and diminished IL-4 and IFN-gamma responses in the chronic disease, demonstrating that C5aR modifies T-helper cell polarization. CONCLUSIONS:: C5aR exerts detrimental functions in acute colitis, strongly supporting the idea that a C5aR-antagonist might be useful for IBD treatment. However, since the absence of C5aR was no longer protective and in some regards disadvantageous in chronic IBD, future studies should address the efficacy and the possible side effects of a sustained antagonist treatment. (Inflamm Bowel Dis 2009;).
• 12.90

  Impact points

  Microbiome Analysis in the Esophagus.

  Sebastian Suerbaum

  Gastroenterology. 07/2009;
• 3.94

  Impact points

  The Helicobacter pylori anti-sigma factor FlgM is predominantly cytoplasmic and cooperates with the flagellar basal body protein FlhAC.

  Melanie Rust, Sophie Borchert, Eike Niehus, Sarah A. Kuehne, Eugenia Gripp, Afrodita Bajceta, Jonathan L. McMurry, Sebastian Suerbaum, Kelly T Hughes, Christine Josenhans

  Journal of bacteriology. 06/2009;

  H. pylori requires flagellar motility and orientation to persist actively in its habitat. A particular feature of flagella in most Helicobacter species including H. pylori is a membraneous flagellar sheath. The anti-sigma factor FlgM of H. pylori is unusual, since it lacks an N-terminal domain prese... [more] H. pylori requires flagellar motility and orientation to persist actively in its habitat. A particular feature of flagella in most Helicobacter species including H. pylori is a membraneous flagellar sheath. The anti-sigma factor FlgM of H. pylori is unusual, since it lacks an N-terminal domain present in other FlgM homologs, e.g. FlgM of Salmonella, whose regulatory function is intimately coupled to its secretion through the flagellar type III secretion system. The aim of the present study was to characterize the localization and secretion of the short H. pylori FlgM in the presence of a flagellar sheath and to elucidate its interaction with other flagellar proteins, such as the basal body protein FlhA which was previously shown to cooperate with FlgM for regulation. H. pylori FlgM was only released into the medium in minor amounts in wild type bacteria, where the bulk amount of the protein was retained in the cytoplasm. Some FlgM was detected in the flagellar fraction. FlgM was expressed in flhA mutants and was less soluble and differentially localized in bacterial fractions of the flhA mutant in comparison to wild type bacteria. FlgM-GFP (green fluorescent protein) and FlgM-V5 translational fusions were generated and expressed in H. pylori. FlgM displayed a predominantly polar distribution and interacted with the C-terminal domain of FlhA (FlhAC). We suggest that, in H. pylori, FlgM secretion may not be paramount for its regulatory function and that protein interactions at the flagellar basal body may determine the turnover and localization of functional FlgM.
• 1.19

  Impact points

  [S3-Guideline "Helicobacter Pylori and Gastroduodenal Ulcer Disease"]

  W Fischbach, P Malfertheiner, J Hoffmann, W Bolten, J Bornschein, O Götze, W Höhne, M Kist, S Koletzko, J Labenz, [......], U Peitz, J Preiß, C Prinz, U Rosien, W Schmidt, A Schwarzer, S Suerbaum, A Timmer, G Treiber, M Vieth

  Zeitschrift fur Gastroenterologie. 02/2009; 47(1):68-102.

  This guideline updates a prior concensus recommendation of the German Society for Digestive and Metabolic Diseases (DGVS) from 1996. It was developed by an interdisciplinary cooperation with representatives of the German Society for Microbiology, the Society for Pediatric Gastroenterology and Nutrit... [more] This guideline updates a prior concensus recommendation of the German Society for Digestive and Metabolic Diseases (DGVS) from 1996. It was developed by an interdisciplinary cooperation with representatives of the German Society for Microbiology, the Society for Pediatric Gastroenterology and Nutrition (GPGE) and the German Society for Rheumatology. The guideline is methodologically based on recommendations of the Association of the Scientific Medical Societies in Germany (AWMF) for providing a systematic evidence-based consensus guideline of S 3 level and has also implemented grading criteria according to GRADE (Grading of Recommendations Assessment, Development and Evaluation). Clinical applicability of study results as well as specifics for Germany in terms of epidemiology, antibiotic resistance status, diagnostics and therapy were taken into account.