In Vivo Targets of Pasteurella Multocida Toxin

TY - JOUR

T1 - In Vivo Targets of Pasteurella Multocida Toxin

AU - Banu, Arshiya

AU - Lax, Alistair J.

AU - Grigoriadis, Agamemnon E.

PY - 2020/4/15

Y1 - 2020/4/15

N2 - 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.

AB - 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.

KW - Pasteurella multocida toxin; G-proteins; proliferation; QE antibody; Ki67; pHH3; β-catenin

KW - β-catenin

KW - Pasteurella multocida toxin

KW - PHH3

KW - Proliferation

KW - Ki67

KW - G-proteins

KW - QE antibody

UR - http://www.scopus.com/inward/record.url?scp=85083468997&partnerID=8YFLogxK

U2 - 10.3390/ijms21082739

DO - 10.3390/ijms21082739

M3 - Article

SN - 1422-0067

VL - 21

SP - 2739

EP - 2750

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

IS - 8

M1 - 2739

ER -