Dr. M. Böhm (bis 31.12.19)
Research Group Böhm
Food-borne infections by Campylobacter jejuni are the major cause of human bacterial gastroenteritis, and may be responsible for as many as 400-500 million cases worldwide every year. Disease outcomes vary from mild, non-inflammatory, self-limiting diarrhea to severe, inflammatory, bloody diarrhea and abdominal pain lasting for several weeks, but C. jejuni is also associated with more severe sequelae such as the development of reactive arthritis and peripheral neuropathies, the Miller-Fisher and Guillain-Barrè syndromes, in some individuals. Major challenges are the lack of effective control schemes for C. jejuni in the food chain and a relatively poor understanding of basic mechanisms underlying host-pathogen interactions. Despite the array of bacterial virulence factors reported in the past, their potential role in pathogenesis is often controverse in the literature and still not fully clear. For example, it remained widely unknown which of the proposed C. jejuni factors are typical adhesins or not, and which disease-related signaling pathways are regulated by these factors. Recently, we have identified a novel C. jejuni virulence factor directly interacting with host cells, high temperature requirement A (HtrA), a surface exposed serine protease. Having established a series of important molecular tools and methods in our previous studies, we aim to gain a detailed understanding of the molecular mechanisms underlying specific HtrA functions in cell adhesion, invasion and host signaling during infection with C. jejuni in vitro and in vivo. We are performing a deletion mutagenesis across the entire HtrA protein to identify the host cell binding domain. This will be further analysed using in vitro binding and cell invasion assays, quantitative immunoprecipitation combined with knockdown (QUICK), signaling methods, confocal microscopy and live cell imaging as well as short- and longterm mouse infections experiments. This approach will allow us to reconstruct the sequence of events occurring at the pathogen–host cell interface, and to identify novel key pathogenicity determinants. Further progress both in understanding of the biological significance of bacterial virulence factors and the nature of bacterial interactions with its host will lead to new strategies for detecting, controlling, and reducing Campylobacter infections. In a longterm perspective, this could help both to decrease the burden of Campylobacter-induced human illness and to reduce clinical expenses.
- Boehm M, Simson D, Escher U, Schmidt A-M, Bereswill S, Tegtmeyer N, Backert S, Heimesaat MM (2018) Function of serine protease HtrA in the lifecycle of the foodborne pathogen Campylobacter jejuni. Eur J Microbiol Immunol. 8(3), 70-77.
- Harrer A, Boehm M, Backert S, Tegtmeyer N (2017) Overexpression of serine protease HtrA enhances disruption of adherens junctions, paracellular transmigration and type IV secretion of CagA by Helicobacter pylori. Gut Pathogens. 9:40.
- Tegtmeyer N, Wessler S, Necchi V, Rohde M, Harrer A, Rau TT, Asche CI, Boehm M, Loessner H, Figueiredo C, Naumann M, Palmisano R, Solcia E, Ricci V, Backert S (2017) Helicobacter pylori Employs a Unique Basolateral Type IV Secretion Mechanism for CagA Delivery. Cell Host Microbe 22(4):552-560.
- Boehm M, Tegtmeyer N, Harrer A, Skórko-Glonek J, Backert S (2017) Expression of Helicobacter pylori serine protease HtrA in Campylobacter jejuni reveals a crucial function in oxygen stress resistance, heat tolerance and epithelial barrier disruption. Immunol. and Serum Biol. [doi.org/10.15436/2471-5891.17.009].
- Backert S, Tegtmeyer N, Ó Cróinín T, Boehm M, Heimesaat MM (2016) Human Campylobacteriosis. First chapter, In: Klein G, Editor. Campylobacter-features, detection, and prevention of foodborne disease. London: Elsevier, Academic Press 1–25.
- Schmidt TP, Perna AM, Fugmann T, Böhm M, Hiss J, Haller S, Götz C, Tegtmeyer N, Rau TT, Neri D, Backert S, Schneider G, Wessler S. (2016) Identification of E-cadherin signature motifs functioning as cleavage sites for Helicobacter pylori Sci Rep. 6: 23264.
- Perna AM, Rodrigues T, Schmidt TP, Boehm M, Stutz K, Reker D, Pfeiffer B, Altmann KH, Backert S, Wessler S, Schneider G. (2015) Fragment-Based De Novo Design Reveals a Small-Molecule Inhibitor of Helicobacter Pylori HtrA. Angew Chem Int Ed. 54: 10244-10248.
- Boehm M, Lind J, Backert S, Tegtmeyer N. (2015) Campylobacter jejuni serine protease HtrA plays an important role in heat tolerance, oxygen resistance, host cell adhesion,invasion, and transmigration. Eur J Microbiol Immunol (Bp). 5: 68-80.
- Heimesaat MM, Fischer A, Alutis M, Grundmann U, Boehm M, Tegtmeyer N, Göbel UB, Kühl AA, Bereswill S & Backert S (2014) The impact of serine protease HtrA in apoptosis, intestinal immune responses and extra-intestinal histopathology during Campylobacter jejuni infection of infant mice. Gut Pathogens 6.16.
- Heimesaat MM, Alutis M, Grundmann U, Fischer A, Tegtmeyer N, Böhm M, Kühl AA, Göbel UB, Backert S & Bereswill S (2014) The role of serine protease HtrA in acute ulcerative enterocolitis and extra-intestinal immune responses during Campylobacter jejuni infection of gnotobiotic IL-10 deficient mice. Front in Cell. Infect. Microbiol. 4:77.
- Boehm M, Haenel I, Hoy B, Brøndsted L, Smith TG, Hoover T, Wessler S & Tegtmeyer N (2013) Extracellular secretion of protease HtrA from Campylobacter jejuni is highly efficient and independent of its protease activity and flagellum. Eur. J. Microbiol. Immunol. 3:3 163-173.
- Backert S, Boehm M, Wessler S & Tegtmeyer N (2013) Transmigration route of Campylobacter jejuni across polarized intestinal epithelial cells: paracellular, transcellular or both? Cell Commun. and Signal. 11:72.
- Boehm M, Hoy B, Rohde M, Tegtmeyer N, Bæk KT, Oyarzabal OA, Brøndsted L, Wessler S & Backert S (2012) Rapid paracellular transmigration of Campylobacter jejuni across polarized epithelial cells without affecting TER: role of proteolytic-active HtrA cleaving E-cadherin but not fibronectin. Gut Pathogens 4:3.
- Hoy B, Geppert T, Boehm M, Reisen F, Plattner P, Gadermaier G, Sewald N, Ferreira F,Briza P, Schneider G, Backert S & Wessler S (2012) Distinct roles of secreted HtrA proteases from Gram-negative pathogens in cleaving the junctional protein and tumor suppressor E-cadherin. J. Biol. Chem. 287 (13): 10115-10120.
- Krause-Gruszczynska* M, Boehm* M, Rohde M, Tegtmeyer N, Takahashi S, Buday L,Oyarzabal OA & Backert S (2011) The signaling pathway of Campylobacter jejuni induced Cdc42 activation: Role of fibronectin integrin beta1, tyrosine kinases and guanine exchange factor Vav2. Cell Commun. and Signal. 9:32.
- Boehm M, Krause-Gruszczynska M, Rohde M, Tegtmeyer N, Takahashi S, Oyarzabal OA & Backert S (2011) Role of fibronectin, integrin beta1, FAK, Tiam-1, DOCK180 in activating Rho GTPase Rac1. Front in Cell. Infect. Microbiol. 1:17.