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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:

Faber E, Gripp E, Maurischat S, Kaspers B, Tedin K, Menz S, Zuraw A, Kershaw O, Yang I, Rautenschlein S, Josenhans C. Novel immunomodulatory flagellin-like protein FlaC in Campylobacter jejuni and other Campylobacterales. mSphere 2015; 1:e0028-15. DOI: 10.1128/mSphere.00028-15

 

Behrens W, Schweinitzer T, Bal J, Dorsch M, Bleich A, Kops F, Brenneke B, Didelot X, Suerbaum S, Josenhans C. Role of energy sensor TlpD of Helicobacter pylori in gerbil colonization and genome analyses after adaptation in the gerbil. Infect Immun. 2013; 81:3534-51.

 

Bartonickova L, Sterzenbach T, Nell S, Kops F, Schulze J, Venzke A, Brenneke B, Bader S, Gruber AD, Suerbaum S, Josenhans C. Hcp and VgrG1 are secreted components of the Helicobacter hepaticus type VI secretion system and VgrG1 increases the bacterial colitogenic potential. Cell Microbiol. 2013 15:992-1011.

 

Gripp E, Hlahla D, Didelot X, Kops F, Maurischat S, Tedin K, Alter T, Ellerbroek L, Schreiber K, Schomburg D, Janssen T, Bartholomäus P, Hofreuter D, Woltemate S, Uhr M, Brenneke B, Grüning P, Gerlach G, Wieler L, Suerbaum S, Josenhans C. Closely related Campylobacter jejuni strains from different sources reveal a generalist rather than a specialist lifestyle. BMC Genomics. 2011; 12:584.

 

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 2011; 301:213-224.

 

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.

 

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. (Review)

 

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

 

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

 

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.

 

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.

 

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.

 

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.


Funding:

 

DFG, DZIF/BMBF, BMBF, EU

faculty member of the Hannover Biomedical Research School of Hannover Medical School (Graduate programs ZIB and IRTG 1273 (DFG)


Alumni:

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


Current group