Abstract
Pasteurella multocida produces a 146-kDa protein toxin (Pasteurella multocida toxin, PMT), which stimulates diverse cellular signal transduction pathways by activating heterotrimeric G proteins. PMT deamidates a conserved glutamine residue of the α-subunit of heterotrimeric G proteins that is essential for GTP-hydrolysis, thereby arresting the G protein in the active state. The toxin substrates are Gαq Gα13 and the Gαi-family proteins. Activation of these α-subunits causes stimulation of phospholipase Cβ, Rho-guanine nucleotide exchange factors or inhibition of adenylyl cyclase. This article provides the current knowledge on PMT concerning the structure-function analysis based on the crystal structure and recently elucidated molecular mode of action. Furthermore, the impact of PMT on cellular signaling is discussed.
Highlights
Pasteurella multocida is a Gram negative opportunistic pathogenic bacterium living in the nasal, pharyngeal space of animals
PMT is a 146-kDa protein toxin, encompassing 1,285 amino acid residues [21]. It belongs to a family of dermonecrotic toxins, including the cytotoxic necrotizing factors (CNF1-3) from Escherichia coli and Yersinia pseudotuberculosis (CNFy) and dermonecrotic toxin (DNT) from Bordetella pertussis and B. bronchiseptica and PMT
The elucidation of the crystal structure of the toxin and recognition of Gαi as an additional toxin substrate were pivotal to clarify the molecular mechanism of PMT
Summary
Pasteurella multocida is a Gram negative opportunistic pathogenic bacterium living in the nasal, pharyngeal space of animals. Human infections occur usually by scratches and bites of domesticated animals (e.g., mainly cats and dogs). Contact with salvia is sufficient for colonization of bacteria [1]. P. multocida is of particular importance in livestock management, especially of pigs. The infection of swine with P. multocida leads under special conditions to a atrophic rhinitis that was first. Toxins 2010, 2 described by Franque in 1830 [2]. A main symptom in pigs is the loss of nasal turbinate bones leading to a twisted or shortened snout. The causative agent of atrophic rhinitis is a protein toxin produced by. P. multocida (Pasteurella multocida toxin, PMT) [3,4]
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