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Microbial pathogenesis and genome dynamics

The organisms

Neisseria meningitidis

Mycobacterium tuberculosis

The project



Meningococcal pilus biogenesis

Neisseria meningitidis, the meningococcus, is the causative agent of meningitis. Pili are the primary virulence factor of this exclusive human pathogen. The transport of these macromolecular structures across membranes is performed by a complex machinery. We are characterising the structure-function relationship and interactions of the components involved in this membrane transport.

Genome dynamics and genome maintenance

The genome of the meningococcus, is very unstable. To counteract this high genome instability, there is a need for well-developed DNA repair mechanisms. Our studies on genome instability and components providing genome maintenance in the meningococcal model bacterium are most important for understanding the balance between fitness for survival and disease development.

Genomics in the search for novel signature DNA sequences

We are using our combined expertise on evolutionary phylogeny, prokaryote cell physiology and comparative genomics to identify new signature sequences. We are currently defining new tools to target novel DNA binding proteins.

Intracellular survival of Mycobacterium tuberculosis

Mycobacterium tuberculosis is the cause of tuberculosis. Inside the hostile environment of the macrophage phagolysozome, M. tuberculosis faces unusually harsh challenges. We are studying the mechanisms for genome maintenance and thereby fitness for survival in the world’s biggest bacterial killer.

Goals

Our analysis of surface structures and genome maintenance components and their actions and interactions will provide new insight into bacterial pathogenesis and virulence. In the long run this information will enable us to develop new strategies for prevention and treatment of disease

The type 4 pilus machinery
Click on the picture for a larger version!
You can find an animated version here (330kb)!

Genome stability and variation
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Selected publications

  • Tonjum T, Seeberg E. (2001) Microbial fitness and genome dynamics. Trends Microbiol. 9 (8), 356-358.
  • Collins RF, Davidsen L, Derrick JP, Ford RC, Tonjum T. (2001) Analysis of the PilQ secretin from Neisseria meningitidis by transmission electron microscopy reveals a dodecameric quaternary structure. J Bacteriol. 183 (13), 3825-3832.
  • Tonjum T, Caugant DA, Dunham SA, Koomey M. (1998) Structure and function of repetitive sequence elements associated with a highly polymorphic domain of the Neisseria meningitidis PilQ protein. Mol Microbiol. 29 (1), 111-124.
  • Tonjum T, Koomey M. (1997) The pilus colonization factor of pathogenic neisserial species: organelle biogenesis and structure/function relationships--a review. Gene. 192 (1), 155-163.

Publication list for Dr.T.Tønjum from the US National Library of Medicine (NLM) and PubMed.






(Last updated 2003-05-13 by SAF)