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2 - The mitogenic Pasteurella multocida toxin and cellular signalling

Published online by Cambridge University Press:  15 September 2009

Gillian D Pullinger
Affiliation:
Institute for Animal Health
Alistair J. Lax
Affiliation:
King's College London
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Summary

The Pasteurella multocida toxin (PMT) is produced by some type A and D strains of the Gram-negative bacterium Pasteurella multocida. These bacteria cause several animal infections and can occasionally cause human disease. PMT is the major virulence factor associated with porcine atrophic rhinitis, a non-fatal respiratory infection characterised by loss of the nasal turbinate bones and a twisting or shortening of the snout. However, PMT is highly toxic to animals, being lethal to mice at similar concentrations to diphtheria toxin. Despite these toxic properties, it turns out that PMT has unexpected effects on cells in culture leading to perturbation of several signalling pathways. The consequence of this action is that PMT can affect the regulation of cell growth and differentiation.

PMT IS A MITOGEN

The cellular effects of PMT have been most widely studied on Swiss 3T3 cells, a mouse fibroblast cell line. These cells are useful for studying growth factors since they are contact-inhibited and are readily quiesced by growing to confluence and allowing the cells to deplete the medium of growth factors. Rozengurt et al. (1990) first showed that PMT caused quiescent Swiss 3T3 cells to recommence DNA synthesis. The toxin is highly potent, inducing maximal DNA synthesis at only 1.25 ng/ml (or about 2 pM). This is equivalent to the DNA synthesis induced by 10% foetal bovine serum. Thus, PMT is more mitogenic for this cell type than any known growth factor (Figure 2.1, top panel).

Type
Chapter
Information
Bacterial Protein Toxins
Role in the Interference with Cell Growth Regulation
, pp. 7 - 32
Publisher: Cambridge University Press
Print publication year: 2005

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