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The Bacterial Outer Membrane

Tuesday 23 October 2012

Prof.dr. J.P.M. (Jan) Tommassen
Section Molecular Microbiology, Department of Biology, Utrecht University

Gram-negative bacteria are enveloped by two membranes. We are focusing on the outer membrane, which is in contact with the environment including the immune system of the host. We are studying the structure, function and biogenesis of outer-membrane proteins, many of which play a role in immune evasion. We are also studying the biogenesis of the major lipid component of the outer membrane, lipopolysaccharide (a.k.a. endotoxin), and the modifications it undergoes to prevent signaling by the innate immune system. Gram-negative bacteria have evolved complicated molecular machines for the secretion of proteins into the environment. We are studying the structure and function of these machines and the roles of the secreted proteins in the interactions with the host and between bacteria.

The outer membrane functions as a diffusion barrier and is responsible for the intrinsic resistance of Gram-negative bacteria against many antibiotics. Using our fundamental knowledge of the outer membrane, we are trying to bypass this obstacle by targeting the surface-exposed outer-membrane proteins with novel antimicrobial compounds.

The model organism in most of our studies is Neisseria meningitidis, a strictly human pathogen that causes sepsis and meningitis. No broadly protective vaccine is available as yet. In collaboration with the pharmaceutical industry, we are selecting vaccine candidates which are included in a novel rationally designed vaccine.


Group members:
Jan Tommassen
Margot Koster
Jan Grijpstra
Jesús Arenas
Florian Putker
Ria van Boxtel
Frank Bekkers

Key papers:

Renault, M., R. Tommassen-van Boxtel, M.P. Bos, J.A. Post, J. Tommassen, and M. Baldus. 2012. Cellular solid-state Nuclear Magnetic Resonance spectroscopy. Proc. Natl. Acad. Sci. USA 109:4863-4868.

Tommassen, J. 2010. Assembly of outer membrane proteins in bacteria and mitochondria. Microbiology 156:2587-2596.

Stork, M., M. P. Bos, I. Jongerius, N. de Kok, I. Schilders, V. E. Weynants, J. T. Poolman, and J. Tommassen. 2010. An outer membrane receptor of Neisseria meningitidis involved in zinc acquisition with vaccine potential. PLoS Pathogen. 6:e1000969.

Walther, D.M., D. Papic, M.P. Bos, J. Tommassen, and D. Rapaport. 2009. Signals in bacterial -barrel proteins are functional in eukaryotic cells for targeting to and assembly in mitochondria. Proc. Natl. Acad. Sci. USA 106:2531-2536.

Bos, M.P., V. Robert, and J. Tommassen. 2007. Biogenesis of the Gram-negative bacterial outer membrane. Annu. Rev. Microbiol. 61:191-214.

Robert, V., E. B. Volokhina, F. Senf, M. P. Bos, P. Van Gelder, and J. Tommassen. 2006. Assembly factor Omp85 recognizes its outer membrane protein substrates by a species-specific C-terminal motif. PLoS Biol. 4:1984-1995.

Geurtsen, J., L. Steeghs, H-J. Hamstra, J. ten Hove, A. de Haan, B. Kuipers, J. Tommassen, and P. van der Ley. 2006. Expression of LPS-modifying enzymes PagP and PagL modulates the endotoxic activity of Bordetella pertussis. Infect. Immun. 74:5574-5585.

Rutten, L., J. Geurtsen, W. Lambert, J. J. M. Smolenaers, A. M. Bonvin, A. de
Haan, P. van der Ley, M. R. Egmond, P. Gros, and J. Tommassen. 2006. Crystal structure and catalytic mechanism of the LPS 3-O-deacylase PagL from Pseudomonas aeruginosa. Proc. Natl. Acad. Sci. USA 103:7071-7076.

van Ulsen, P., and J. Tommassen. 2006. Protein secretion and secreted proteins in pathogenic Neisseriaceae. FEMS Microbiol. Rev. 30:292-319.

Bos M.P., B. Tefsen, J. Geurtsen, and J. Tommassen. 2004. Identification of an outer membrane protein required for the transport of lipopolysaccharide to the bacterial cell surface. Proc. Natl. Acad. Sci. USA 101:9417-9422.

Voulhoux, R., M. P. Bos, J. Geurtsen, M. Mols, and J. Tommassen. 2003. Role of a highly conserved bacterial protein in outer membrane protein assembly. Science 299:262-265.