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Molecular biology of cell wall regeneration in L-form bacteria

Objective

Cell wall deficient (L-form) bacteria are thought to be important in various resistant, persistent or chronic infections. L-form cells are highly abnormal in size and shape and are sensitive to osmotic shock but highly resistant to antibiotics that work on the cell wall (e.g. penicillins and cephalosporins). How these unusual cells arise and how they proliferate in the absence of a wall, is poorly understood. The Errington lab recently developed a model system for studying this long standing problem in the tractable model bacterium Bacillus subtilis. A key element of L-form biology that awaits further investigation lies in how these cells revert to the walled state. This reversion or regeneration requires the resumption of cell wall synthesis and the reacquisition of the normal regular rod cell shape. Regeneration is presumably important for the resumption of disease in patients with persistent or recurrent infections. Therefore, blocking regeneration might offer a way of dealing with problem infections. A better understanding of the mechanisms of regeneration might also be important for various biotechnological applications. The aims of this proposal are as follows. First, to use state of the art imaging methods to characterise the poorly understood regeneration process. Second, to attempt to identify mutations that prevent or enhance the rate of regeneration, and characterise the genes affected, so as to understand the process better. The genes identified might provide novel targets for drugs to target persistence. Finally to explore the extent to which regeneration of L-forms can be exploited as a novel vehicle for efficient transformation or genome transplantation processes.

Field of science

  • /natural sciences/biological sciences/molecular biology
  • /natural sciences/biological sciences/microbiology/bacteriology

Call for proposal

FP7-PEOPLE-2010-IEF
See other projects for this call

Funding Scheme

MC-IEF - Intra-European Fellowships (IEF)

Coordinator

UNIVERSITY OF NEWCASTLE UPON TYNE
Address
Kings Gate
NE1 7RU Newcastle Upon Tyne
United Kingdom
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 201 049,60
Administrative Contact
Amanda Gregory (Dr.)