Molecular Biology of Pasteurella multocida Toxin

Orth, J.; Aktories, Klaus

doi:10.1007/82_2012_201

Cited by 19 publications

(20 citation statements)

References 96 publications

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“…PMT is a member of the dermonecrotic toxin family of Gprotein-deamidating toxins, whose molecular mechanism of action has been thoroughly reviewed (201,(484)(485)(486)(487). Mounting evidence suggests that PMT enters mammalian cells (reviewed in reference 486) and exerts its pathogenic effect on cells through modulation of multiple signaling pathways (reviewed in reference 485).…”

Section: Survival In the Host Environmentmentioning

confidence: 99%

Pasteurella multocida: from Zoonosis to Cellular Microbiology

2013

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SUMMARY In a world where most emerging and reemerging infectious diseases are zoonotic in nature and our contacts with both domestic and wild animals abound, there is growing awareness of the potential for human acquisition of animal diseases. Like other Pasteurellaceae , Pasteurella species are highly prevalent among animal populations, where they are often found as part of the normal microbiota of the oral, nasopharyngeal, and upper respiratory tracts. Many Pasteurella species are opportunistic pathogens that can cause endemic disease and are associated increasingly with epizootic outbreaks. Zoonotic transmission to humans usually occurs through animal bites or contact with nasal secretions, with P. multocida being the most prevalent isolate observed in human infections. Here we review recent comparative genomics and molecular pathogenesis studies that have advanced our understanding of the multiple virulence mechanisms employed by Pasteurella species to establish acute and chronic infections. We also summarize efforts being explored to enhance our ability to rapidly and accurately identify and distinguish among clinical isolates and to control pasteurellosis by improved development of new vaccines and treatment regimens.

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Section: Survival In the Host Environmentmentioning

confidence: 99%

Pasteurella multocida: from Zoonosis to Cellular Microbiology

2013

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“…PMT activates various heterotrimeric G proteins (7,8). Recently, we identified the molecular mechanism of the toxin as a deamidation of the ␣-subunits of heterotrimeric G proteins (9).…”

mentioning

confidence: 99%

“…The 146-kDa toxin PMT is a one-chain toxin comprising 1,285 amino acids (aa) (7). Different domains of PMT are involved in cell uptake and intracellular action.…”

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confidence: 99%

Pasteurella multocida Toxin as a Transporter of Non-Cell-Permeating Proteins

et al. 2013

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bThe protein toxin Pasteurella multocida toxin (PMT) is the causative agent of atrophic rhinitis in pigs, leading to atrophy of the nasal turbinate bones by affecting osteoblasts and osteoclasts. The mechanism of PMT-induced intoxication is a deamidation of ␣-subunits of heterotrimeric G proteins, including G␣ q , G␣ 13 , and G␣ i , thereby causing persistent activation of the G proteins. Here we utilized PMT as a transporter of the non-cell-permeating A domain of diphtheria toxin (DTa). Fusion proteins of PMT and DTa ADP-ribosylated elongation factor 2, the natural target of diphtheria toxin, leading to cell toxicity. PMT-DTa effects were competed by PMT, indicating binding to the same cell surface receptor. Fluorescently labeled PMT-DTa and PMT colocalized with specific markers of early and late endosomes. Bafilomycin A, which inhibits vacuolar H ؉ -ATPase, blocked PMT-DTainduced intoxication of HEK-293 cells. By constructing various PMT-DTa chimeras, we identified a minimal region of PMT necessary for uptake of DTa. The data suggest that PMT is able to transport cargo proteins into eukaryotic cells by utilizing the PMT-specific uptake route.

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“…Typhimurium effector protein of the type III secretion system SPI-2 (Bhaskaran and Stebbins, 2012) and PMT, a toxin from Pasteurella multocida, which was recognized to activate heterotrimeric G proteins by deamidation (Kitadokoro et al, 2007;Orth et al, 2009;Orth and Aktories, 2012). Similar as PMT, the deamidase domain of PaTox activates the a-subunits of the heterotrimeric Ga i and Ga q proteins by deamidation of Gln204 and Gln209, respectively .…”

Section: The Deamidase Domain Of Patoxmentioning

confidence: 96%