In Vivo Targets of Pasteurella Multocida Toxin

Int J Mol Sci. 2020 Apr 15;21(8):2739. doi: 10.3390/ijms21082739.

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.

Keywords: G-proteins; Ki67; Pasteurella multocida toxin; QE antibody; pHH3; proliferation; β-catenin.

MeSH terms

  • Animals
  • Bacterial Proteins / genetics
  • Bacterial Proteins / toxicity*
  • Bacterial Toxins / genetics
  • Bacterial Toxins / toxicity*
  • Cell Proliferation / drug effects*
  • Endometrium / drug effects
  • Endometrium / metabolism
  • Female
  • GTP-Binding Protein alpha Subunits, Gq-G11 / metabolism*
  • Immunohistochemistry
  • Mice
  • Pasteurella multocida / metabolism*
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Signal Transduction / drug effects*
  • Spleen / drug effects
  • Spleen / metabolism
  • Thymus Gland / drug effects
  • Thymus Gland / metabolism
  • Uterus / drug effects
  • Uterus / metabolism
  • beta Catenin / metabolism

Substances

  • Bacterial Proteins
  • Bacterial Toxins
  • Pasteurella multocida toxin
  • Recombinant Proteins
  • beta Catenin
  • GTP-Binding Protein alpha Subunits, Gq-G11