Pasteurella multocida toxin

The major virulence factor of Pasteurella multocida responsible for atrophic rhinitis, pneumonia-like respiratory disease, and dermonecrosis is a monomeric 1285 amino acid protein toxin (PMT, Pasteurella multocida toxin) produced primarily by capsular type D and some capsular type A strains. Recently, the molecular mechanism of PMT was defined as the specific deamidation of a crucial glutamine residue in the -subunit of heterotrimeric G proteins. As a consequence of PMT action, the G proteins are constitutively activated, which results in modulation of multiple downstream signaling pathways leading to pleiotropic cellular effects, including mitogenesis and proliferation, as well as the manipulation of cell differentiation and other cell fate decisions involved in adipogenesis, osteogenesis, and immunity. This chapter reviews what is currently known about the structure, molecular mechanism, and substrate specificity of PMT, as well as its interaction with and effects on mammalian cells and its role in pathogenesis.