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In Vivo Targets of Pasteurella Multocida Toxin

Research output: Contribution to journalArticlepeer-review

Original languageEnglish
Article number2739
Pages (from-to)2739-2750
JournalInternational Journal of Molecular Sciences
Volume21
Issue number8
Early online date15 Apr 2020
DOIs
Accepted/In press14 Apr 2020
E-pub ahead of print15 Apr 2020
Published15 Apr 2020

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King's Authors

Abstract

Many Pasteurella multocida strains are carried as commensals, while some cause disease in animals and humans. Some type D strains cause atrophic rhinitis in pigs, where the causative agent is known to be the Pasteurella multocida toxin (PMT). PMT activates three families of G-proteins—G q/11, G 12/13, and G i/o —leading to cellular mitogenesis and other sequelae. The effects of PMT on whole animals in vivo have been investigated previously, but only at the level of organ-specific pathogenesis. We report here the first study to screen all the organs targeted by the toxin by using the QE antibody that recognizes only PMT-modified G-proteins. Under our experimental conditions, short-term treatment of PMT is shown to have multiple in vivo targets, demonstrating G-alpha protein modification, stimulation of proliferation markers and expression of active β-catenin in a tissue-and cell-specific manner. This highlights the usefulness of PMT as an important tool for dissecting the specific roles of different G-alpha proteins in vivo.

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