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Work group of Prof. Dr. Josenhans

 

 

Research focus and selected publications

 

 

Prof. Dr. Christine Josenhans started as a group leader at Hannover Medical School (MHH), in the Institute for Medical Microbiology, in 2004, after finishing Habilitation in Microbiology at the University of Wuerzburg, Germany.


Main research area of the group is

"Cellular Microbiology in the Gastrointestinal Tract"


Different topics studied in the group of Christine Josenhans are the different modes of interaction of bacteria (pathogens and commensals) in the gastro-intestinal tract with the mammalian host (e.g. human, mouse), and with various isolated host cells, in particular epithelial cells. Bacteria and host organism can coexist exclusively in a carefully balanced dynamic equilibrium, which is established by communication mechanisms between bacteria and host, and is maintained through continuous adaptation between both interaction “partners” during evolution and infection. Current knowledge makes dysregulation of this balance between bacteria and host, among other factors, responsible for the advent, maintenance and aggravation of chronic infectious diseases and their sequelae, ranging from acute infectious inflammation to malignant tumours or the promotion of autoimmune disease. E. g. Helicobacters, bacterial species persistently living in the stomach and gut of various animals, have lived closely and coevolved with their human and mammalian hosts for several 10,000 years, but the human pathogenic species, Helicobacter pylori, which currently holds infected half of the world population and persists lifelong in the stomach of its human host, is causing severe disease in a proportion (10% to 20%) of infected humans, probably promoted by host susceptibility and bacterial virulence factors, but possibly exacerbated in modern times because of severe changes in living, nutrition, hygiene and community-inherent conditions.

Some bacteria are able to promote or directly cause cancer. As is known so far, one of the most important bacterial groups in that respect are also members of the genus Helicobacter, which persistently and actively colonize their vertebrate hosts for a full lifetime of the host. Our main interest is to understand how these bacteria manage to persistently colonize their habitat without eliciting a productive immune defence, and how some of them may contribute to malignant transformation and carcinogenesis. This understanding may have far-reaching consequences as to how we perceive pathogenesis, the pathogenic potential of diverse bacterial strains, the dynamic borderline between commensalism, harmless persistent colonization and pathogenicity, and bacterial cancerogenesis, and may help to develop novel, more specific, therapeutic approaches or vaccines against some chronic persistent pathogenic bacteria.

Concerning the part of the host or the bacteria host-interaction, we investigate the interaction of bacteria and bacterial immune interacting products with mammalian cell receptors of the innate immune system and immune defense mechanisms, and processes which determine and modulate the signal transduction and gene regulation in bacteria and host cells ("crosstalk" between bacterium and host).

Further topics of the group deal with specific bacterial properties, in particular mechanisms contributing to virulence, mainly of Helicobacter species and related bacteria. Bacterial characteristics we study comprise complex bacterial secretion systems (type III and type IV secretion apparatus) used by bacteria to export proteins and other molecules, to achieve bacterial motility by the flagellar organelle, and to enable bacterial behavior and oriented motility (chemotaxis). We also look closely at adhesion mechanisms, and immune modulatory properties of these bacteria. Projects which focus on the bacterial side also include bacterial gene regulation, bacterial signal transduction, and the function of bacterial sensors for environmental signals.

High throughput methods to investigate bacterial and eucaryotic (human, mouse) gene regulation, e. g. whole genome DNA microarrays, were developed and established in the group in collaboration with others, and are currently used to answer questions relevant to the research areas addressed above.


Selected publications:

Suerbaum S, Josenhans C, Sterzenbach T, Drescher B, Brandt P, Bell M, Droege M, Fartmann B, Ge Z, Hörster A, Holland R, Klein K, König J, Macko L, Mendz G, Nyakatura G, Schauer DB, Shen Z, Weber J, Frosch M, Fox JG.  The complete genome sequence of the carcinogenic bacterium Helicobacter hepaticus. Proc Natl Acad Sci USA 2003; 100:7901-6.

Lee SK, Stack A, Katzowitsch E, Aizawa SI, Suerbaum S, Josenhans C. Helicobacter pylori flagellins have very low intrinsic activity to stimulate human gastric epithelial cells via TLR5. Microbes Infect 2003; 5:1345-56.

Schreiber S, Stüben M, Groll C, Scheid P, Hanauer G, Werling H-O, Josenhans C, Suerbaum S. The spatial orientation of Helicobacter pylori in the gastric mucus. Proc Natl Acad Sci 2004; 101:5024-9.

Niehus E, Gressmann H, Ye F, Schlapbach R, Dehio M, Dehio C, Stack A, Meyer TF, Suerbaum S, Josenhans C. Genome-wide analysis of transcriptional hierarchy and feedback regulation in the flagellar system of Helicobacter pylori. Mol Microbiol 2004; 52:947-61.

Schmausser B, Josenhans C, Endrich S, Suerbaum S, Sitaru C, Androulis M, Brändlein S, Rieckmann P, Müller-Hermelink HK, Eck M. CXCR1 and CXCR2 expression on human neutrophils is downregulated by Helicobacter pylori: a new pathomechanism in H. pylori infection? Infect Immun 2004; 72:6773-9.

Schmausser B, Andrulis M, Endrich S, Lee SK, Josenhans C, Müller-Hermelink HK, Eck M. Expression and subcellular distribution of toll-like receptors TLR4, TLR5 and TLR9 on the gastric epithelium in Helicobacter pylori infection. Clin Exp Immunol 2004; 136:521-6.

Schreiber S, Bücker R, Groll C, Baptista M, Garten D, Scheid P, Friedrich S, Gatermann S, Josenhans C, Suerbaum S. Rapid loss of motility of Helicobacter pylori in the gastric lumen in vivo. Infect Immun 2005; 73(3):1584-9.

Andrzejewska J, Lee SK, Olbermann P, Lotzing N, Katzowitsch E, Linz B, Achtman M, Kado CI, Suerbaum S, Josenhans C. Characterization of the pilin ortholog of the Helicobacter pylori type IV cag pathogenicity apparatus, a surface-associated protein expressed during infection. J Bacteriol 2006; 188:5865-77.

Ye F, Brauer T, Niehus E, Drlica K, Josenhans C, Suerbaum S. Flagellar and global gene regulation in Helicobacter pylori modulated by changes in DNA supercoiling. Int J Med Microbiol. 2007; 297:65-81.

Sterzenbach T, Lee SK, Brenneke B, von Goetz F, Schauer DB, Fox JG, Suerbaum S, Josenhans C. Inhibitory effect of enterohepatic Helicobacter hepaticus on innate immune responses of mouse intestinal epithelial cells. Infect Immun 2007; 75:2717-28.

Suerbaum S, Josenhans C. Helicobacter pylori evolution and phenotypic diversification in a changing host. Nat Rev Microbiol 2007; 5:441-52. Review.

Schweinitzer T, Mizote T, Ishikawa N, Dudnik A, Inatsu S, Schreiber S, Suerbaum S, Aizawa S, Josenhans C. Functional characterization and mutagenesis of the proposed behavioral sensor TlpD of Helicobacter pylori. J Bacteriol 2008; 190:3244-55.

Ge Z, Sterzenbach T, Whary MT, Rickman BH, Rogers AB, Shen Z, Taylor NS, Schauer DB, Josenhans C, Suerbaum S, Fox JG. Helicobacter hepaticus HHGI1 is a pathogenicity island associated with typhlocolitis in B6.129-IL10 tm1Cgn mice. Microbes Infect 2008;10:726-33.

Sterzenbach T, Bartonickova L, Behrens W, Brenneke B, Schulze J, Kops F, Chin EY, Katzowitsch E, Schauer DB, Fox JG, Suerbaum S, Josenhans C. Role of the Helicobacter hepaticus flagellar sigma factor FliA in gene regulation and murine colonization. J Bacteriol 2008; 190:6398-408.

Reeves EP, Ali T, Leonard P, Hearty S, O'Kennedy R, May FE, Westley BR, Josenhans C, Rust M, Suerbaum S, Smith A, Drumm B, Clyne M. Helicobacter pylori lipopolysaccharide interacts with TFF1 in a pH-dependent manner. Gastroenterology 2008;135:2043-54.

Rust M, Borchert S, Niehus E, Kuehne SA, Gripp E, Bajceta A, McMurry JL, Suerbaum S, Hughes KT, Josenhans C. The Helicobacter pylori anti-sigma factor FlgM is predominantly cytoplasmic and cooperates with the flagellar basal body protein FlhA. J Bacteriol 2009; 191:4824-34.

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 gastric pathogen. BMC Genomics 2010; 11:164.

Schweinitzer T, Josenhans C. Bacterial energy taxis: a global strategy? Arch Microbiol 2010; 192(7):507-20.

Nell S, Suerbaum S, Josenhans C. The impact of the microbiota on the pathogenesis of IBD: lessons from mouse infection models. Nat Rev Microbiol 2010; 8:564-77.

Olbermann P, Josenhans C, Moodley Y, Uhr M, Stamer C, Vauterin M, Suerbaum S, Achtman M, Linz B. A global overview of the genetic and functional diversity in the Helicobacter pylori cag pathogenicity island. PLoS Genet 2010; 6:e1001069.

Coombs N, Sompallae R, Olbermann P, Gastaldello S, Göppel D, Masucci MG, Josenhans C. Helicobacter pylori affects the cellular deubiquitinase USP7 and ubiquitin-regulated components TRAF6 and the tumour suppressor p53. Int J Med Microbiol 2010; Dec 3. [Epub ahead of print]


Research grants:

We thank the German Research Council (DFG) and the German Federal Ministry of Education and Research (BMBF) and the EU (INCA FP6 project; ERAnet Pathogenomics) for funding.

Faculty Member of MHH-Hannover Biomedical Research School (graduate programs ZIB and DFG IRTG1273)


Alumni:

Dr. rer. nat. Eike Niehus (PhD)
Dr. rer. nat. Sae-Kyung Lee (PhD)
Dr. rer. nat. Anna Leybo (PhD)
Dr. rer. nat. Patrick Olbermann (PhD)
Dr. rer. nat. Melanie Rust (PhD)
Dr. rer. nat. Tobias Schweinitzer (PhD)
Dr. rer. nat. Torsten Sterzenbach (PhD)
Dr. rer. nat. Fang Ye (PhD)
Dipl.-Biotechnol. Ms Sc Sophie Borchert
Afrodita Bajceta
Verena Ryan


Current group