Genome and population dynamics during chronic infection with Helicobacter pylori

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The infection with the stomach bacterium Helicobacter pylori is one of the most common infections of human. More than one half of the world population is infected with this pathogen. H. pylori infection is frequently acquired in childhood and persists for decades, such that H. pylori is a particularly characteristic example of a chronic infection, the overarching theme of this collaborative research center. Not all H. pylori infected persons suffer from consequences of the infection: approximately 85 percent will never develop any symptoms. Ten to fifteen percent of infected individuals will develop either stomach ulcers or ulcers of the duodenum. One percent will develop the most dangerous complication of H. pylori infection, stomach cancer. Due to the high number of infected persons, H. pylori causes about 800,000 new cases of stomach cancer per year.

It has been known for more than 30 years, that H. pylori bacteria from unrelated patients differ from each other. Every patient carries his/her own individual H. pylori strain, or even multiple strains. H. pylori diversity is thus similar to that of human fingerprints.

The research group around Sebastian Suerbaum aims at elucidating the molecular mechanism that cause the extremely high genetic diversity of H. pylori. They want to clarify how the high variability of these bacteria contributes to the course of H. pylori infection.

Scientific work programme

The research group uses different high throughput sequencing technologies (Next Generation Sequencing) to decipher H. pylori genome sequences. To understand the mechanism that generate genetic diversity, we sequence the isolates from diverse patients, and from different areas of the stomach of one individual.

Furthermore, we study isolates cultures from the same human individual at different time points several years apart, with the aim to study whether the bacteria adapt to their individual human carrier. The researchers use the Illumina MiSeq technology for the analysis of large numbers of H. pylori isolates. This technology usually assembles the genomes in an average of 25 fragments (contigs). The Single Molecule, Real-Time (SMRT) sequencing technology (Pacific Biosciences) is used to generate complete (finished) genome sequences, where the complete circular chromosome is sequenced as one continuous sequence. Due to the higher cost of this technology, only selected strains can be sequenced by SMRT technology, and a combination of both methods permits optimal throughput and a sufficient number of finished reference genomes. Genome sequencing is combined with experimental genetic and biochemical research approaches. We construct mutants where selected H. pylori genes have been inactivated, and study the effect of such mutations on the ability of H. pylori to generate genetic diversity.

This will enable the elucidation of the molecular mechanisms generating mutations in H. pylori and their exchange between strains by recombination. One further topic studied in this project is the epigenetics of H. pylori. SMRT sequencing permits to identify bases in the bacterial genome that have undergone modification by methylation. H. pylori change their methylation pattern during chronic infection, and the research group studies the consequences of such methylation changes for the infection.

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Sebastian Suerbaum is talking about his research at CRC 900

Sebastian Suerbaum has been part of the CRC since it was founded in 2010. His project A1 focuses on investigations into the genetic variability of H. pylori and the link between this genetic diversity and the course of chronic infections. Together with Professor Tümmler Professor Suerbaum also leads project Z1, which offers high-throughput sequencing and bioinformatics as a service for the whole CRC. Professor Suerbaum is also vice-speaker of the CRC.

Publications of the project A1

  • Estibariz I, Overmann A, Ailloud F, Krebes J, Josenhans C, Suerbaum S. Nell S, Estibariz I, Krebes J, Bunk B, Graham DY, Overmann J, Song Y, Spröer C, Yang I, Wex T, Korlach J, Malfertheiner P, Suerbaum S. Nucleic Acids Res. 2019 Mar 18;47(5):2336-2348.
  • Genome and Methylome Variation in Helicobacter pylori With a cag Pathogenicity Island During Early Stages of Human Infection. Nell S, Estibariz I, Krebes J, Bunk B, Graham DY, Overmann J, Song Y, Spröer C, Yang I, Wex T, Korlach J, Malfertheiner P, Suerbaum S. Gastroenterology. 2017 Oct 21. pii: S0016-5085(17)36273-X.
  • Helicobacter pylori Adapts to Chronic Infection and Gastric Disease via pH-Responsive BabA-Mediated Adherence. Bugaytsova J, Björnham O, Chernov YA, Gideonsson P, Henriksson S, Mendez M, Sjöström R, Mahdavi J, Shevtsova A, Ilver D, Moonens K, Quintana-Hayashi MP, Moskalenko R, Aisenbrey C, Bylund G, Schmidt A, Åberg A, Brännström K, Königer V, Vikström S, Rakhimova L, Hofer A, Ögren J, Liu H, Goldman MD, Whitmire JM, Ådén J, Younson J, Kelly CG, Gilman RH, Chowdhury A, Mukhopadhyay AK, Nair GB, Papadakos KS, Martinez-Gonzalez B, Sgouras DN, Engstrand L, Unemo M, Danielsson D, Suerbaum S, Oscarson S, Morozova-Roche LA, Olofsson A, Gröbner G, Holgersson J, Esberg A, Strömberg N, Landström M, Eldridge AM, Chromy BA, Hansen LM, Solnick JV, Lindén SK, Haas R, Dubois A, Merrell DS, Schedin S, Remaut H, Arnqvist A, Berg DE, Borén T. Cell Host Microbe. 2017 Mar 8;21(3):376-389.

  • Genome-wide analysis of chromosomal import patterns after natural transformation of Helicobacter pylori. Bubendorfer S, Krebes J, Yang I, Hage E, Schulz TF, Bahlawane C, Didelot X, Suerbaum S. Nat Commun. 2016 Jun 22;7:11995.
  • Different gastric microbiota compositions in two human populations with high and low gastric cancer risk in Colombia. Yang I, Woltemate S, Piazuelo MB, Bravo LE, Yepez MC, Romero-Gallo J, Delgado AG, Wilson KT, Peek RM, Correa P, Josenhans C, Fox JG, Suerbaum S. Sci Rep. 2016 Jan 5;6:18594.

  • Dynamics of Lewis b binding and sequence variation of the babA adhesin gene during chronic Helicobacter pylori infection in humans. Nell S, Kennemann L, Schwarz S, Josenhans C, Suerbaum S. MBio. 2014 Dec 16;5(6). pii: e02281-14.

  • Bidirectional genomic exchange between Helicobacter pylori strains from a family in Coventry, United Kingdom. Krebes J, Didelot X, Kennemann L, Suerbaum S. Int J Med Microbiol. 2014 Nov;304(8):1135-46.

  • The complex methylome of the human gastric pathogen Helicobacter pylori. Krebes J, Morgan RD, Bunk B, Spröer C, Luong K, Parusel R, Anton BP, König C, Josenhans C, Overmann J, Roberts RJ, Korlach J, Suerbaum S. Nucleic Acids Res. 2014 Feb;42(4):2415-32.

  • Recent acquisition of Helicobacter pylori by Baka pygmies. Nell S, Eibach D, Montano V, Maady A, Nkwescheu A, Siri J, Elamin WF, Falush D, Linz B, Achtman M, Moodley Y, Suerbaum S. PLoS Genet. 2013;9(9):e1003775.

  • Survival in hostile territory: the microbiota of the stomach. Yang I, Nell S, Suerbaum S. FEMS Microbiol Rev. 2013 Sep;37(5):736-61.

  • Genomic evolution and transmission of Helicobacter pylori in two South African families. Didelot X, Nell S, Yang I, Woltemate S, van der Merwe S, Suerbaum S. Proc Natl Acad Sci U S A. 2013 Aug 20;110(34).

  • In vivo sequence variation in HopZ, a phase-variable outer membrane protein of Helicobacter pylori. Kennemann L, Brenneke B, Andres S, Engstrand L, Meyer TF, Aebischer T, Josenhans C, Suerbaum S. Infect Immun. 2012 Dec;80(12):4364-73.

  • Age of the association between Helicobacter pylori and man. Moodley Y, Linz B, Bond RP, Nieuwoudt M, Soodyall H, Schlebusch CM, Bernhöft S, Hale J, Suerbaum S, Mugisha L, van der Merwe SW, Achtman M. PLoS Pathog. 2012;8(5):e1002693.

  • The nucleotide excision repair (NER) system of Helicobacter pylori: role in mutation prevention and chromosomal import patterns after natural transformation. Moccia C, Krebes J, Kulick S, Didelot X, Kraft C, Bahlawane C, Suerbaum S. BMC Microbiol. 2012 May 6;12:67.

  • Genome sequence of Helicobacter pylori hpEurope strain N6. Behrens W, Bönig T, Suerbaum S, Josenhans C. J Bacteriol. 2012 Jul;194(14):3725-6.

  • Helicobacter pylori genome evolution during human infection. Kennemann L, Didelot X, Aebischer T, Kuhn S, Drescher B, Droege M, Reinhardt R, Correa P, Meyer TF, Josenhans C, Falush D, Suerbaum S. Proc Natl Acad Sci U S A. 2011 Mar 22;108(12):5033-8.

  • Molecular evolution of the Helicobacter pylori vacuolating toxin gene vacA. Gangwer KA, Shaffer CL, Suerbaum S, Lacy DB, Cover TL, Bordenstein SR. J Bacteriol. 2010 Dec;192(23):6126-35.

Contact

Prof. Sebastian Suerbaum

Chairman, Dept. of Medical Microbiology and Hospital Epidemiology

Max von Pettenkofer Institute
Ludwig-Maximilians-Universität München
Pettenkoferstr. 9a
80336 München

  +49 89 2180-72800
 suerbaum@mvp.uni-muenchen.de

Homepage of Sebastian Suerbaum´s working group