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—Gq/11, G12/13, and Gi/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.
Highlights
The bacterium Pasteurella multocida is often found as a commensal in the upper respiratory tract of many animals and birds [1]
As Pasteurella multocida toxin (PMT) is one of the most potent mitogens known for eukaryotic cells—in the process, activating a myriad of procarcinogenic signalling pathways—we have previously suggested a potential role for PMT as a potential carcinogen [36,37], how PMT acts in vivo is not well understood
We investigated whether specific tissues that exhibited PMT modification of G-alpha subunits showed any evidence of PMT-induced mitotic activity through immunohistochemical analysis of the expression of the cell cycle markers Ki67 and phospho-Histone H3
Summary
The bacterium Pasteurella multocida is often found as a commensal in the upper respiratory tract of many animals and birds [1]. Toxigenic strains cause atrophic rhinitis in pigs, a condition associated with bone loss as well as systemic proliferative effects [10]. All these effects were shown to be caused by PMT, as they could be reproduced by using purified recombinant PMT [11]. We haveeffect further the systemic effect of mice, PMT by injecting the toxin intofirst time the spectrum of organs targeted by using the QE antibody that recognizes mice, and examining for the first time the spectrum of organs targeted by PMT using the QE antibody the. Weeffects investigated the cellular namely stimulation of celltissues, proliferation active β-catenin, providing a more comprehensive effects of PMT in various namelyand stimulation of cell proliferation and active β‐catenin, providing a more map of the in vivo comprehensive targets of PMT.map of the in vivo targets of PMT
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