Sequence of the dermonecrotic toxin of<i>Pasteurella multocida ssp. multocida</i>

Buys, W.E.C.M.; Smith, Hilde E.; Kamps, A. M. I. E.; Kamp, E. M.; Smits, M.A.

doi:10.1093/nar/18.9.2815

Cited by 42 publications

(32 citation statements)

References 3 publications

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“…The activated GTP-bound G␣ q (Glu-209) subunit then forms a complex with PLC␤ to activate its phospholipase activity. The active PLC␤ catalyzes the hydrolysis of PIP 2 to generate DAG and IP 3 . IP 3 binds to the IP 3 receptor to trigger the release of Ca 2ϩ from the ER.…”

Section: Pmt-mediated Rtk Phosphorylation Exerts No Effect On Mtor Acmentioning

confidence: 99%

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Mammalian Target of Rapamycin Complex 1 (mTORC1) Plays a Role in Pasteurella multocida Toxin (PMT)-induced Protein Synthesis and Proliferation in Swiss 3T3 Cells

Oubrahim

Wong

Wilson

et al. 2013

Journal of Biological Chemistry

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Background: Pasteurella multocida toxin (PMT) is a highly mitogenic bacterial protein whose detailed mechanism is not well understood. Results: PMT deamidates and activates G␣ q/11 leading to mTORC1 activation. Conclusion: G␣ q/11 /PLC␤/PKC-mediated mTORC1 activation is at least partially responsible for PMT-induced cell growth, migration, and proliferation in Swiss 3T3 cells. Significance: Understanding PMT-induced mTORC1 activation could help elucidate mechanisms of oncogene regulation.

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Section: Pmt-mediated Rtk Phosphorylation Exerts No Effect On Mtor Acmentioning

confidence: 99%

“…The gene (toxA) encoding P. multocida toxin (PMT), 3 acquired by horizontal transmission (2), has been cloned and sequenced (3). It is a single polypeptide of 146 kDa whose C-terminal activity domain structure has been solved (4).…”

mentioning

confidence: 99%

Mammalian Target of Rapamycin Complex 1 (mTORC1) Plays a Role in Pasteurella multocida Toxin (PMT)-induced Protein Synthesis and Proliferation in Swiss 3T3 Cells

Oubrahim

Wong

Wilson

et al. 2013

Journal of Biological Chemistry

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“…PAR is characterized by atrophy of the nasal turbinate bones which, in severe cases, can lead to facial distortion. P. multocida strains associated with PAR usually produce a 145-kDa dermonecrotic toxin, which is encoded by the toxA gene (Lax et al, 1990;Buys et al, 1990). This toxin induces osteolysis in the turbinate bones and plays an important role in the pathogenesis of PAR (Kamp & Kimman, 1988).…”

Section: Introductionmentioning

confidence: 99%

“…Detection of the toxA gene was carried out by PCR as described previously (Lichtensteiger et al, 1996) with the exception that different oligonucleotide primers were used. The primers were designed after alignment and comparison of published toxA sequences (Lax et al, 1990;Buys et al, 1990;Petersen, 1990). The oligonucleotide primers were designed to amplify a 1854 bp fragment of toxA between nucleotides 2190 and 4043 (Petersen, 1990); the forward primer was 59-CGTGAACTGCGTACTCAA-39 and the reverse primer was 59-AAGAGGAGGCATGAAGAG-39.…”

mentioning

confidence: 99%

Characterization and comparison of Pasteurella multocida strains associated with porcine pneumonia and atrophic rhinitis

Davies

MacCorquodale

Baillie

et al. 2003

Journal of Medical Microbiology

102

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One hundred and fifty-eight porcine strains of Pasteurella multocida, recovered primarily from cases of pneumonic pasteurellosis or progressive atrophic rhinitis (PAR) in England and Wales, were characterized by determination of their capsular types, presence or absence of the toxA gene and molecular mass heterogeneity of the heat-modifiable (OmpA) and porin (OmpH) proteins. Eighteen groups (clones) of strains were identified on the basis of specific combinations of capsular type, toxA status and outer-membrane protein (OMP)-type. The data provided evidence that different subpopulations of P. multocida are responsible for pneumonia and PAR in pigs. The majority (88 %) of cases of pneumonia were associated exclusively with non-toxigenic capsular type A strains of OMP-types 1.1, 2.1, 3.1 and 5.1 and capsular type D isolates of OMP-type 6.1. These strains were recovered from widespread geographical locations within England and Wales over a 12-year period and represented mostly single sporadic cases. The association of a small number of P. multocida variants with the majority of cases of porcine pneumonia suggests that these strains are not opportunistic pathogens of low virulence but represent primary pathogens with a relatively high degree of virulence. In contrast, the majority (76 %) of cases of PAR were associated with toxAcontaining capsular type D strains of OMP-type 4.1 and capsular type A and D strains of OMP-type 6.1. Toxigenic capsular type A strains associated with PAR and non-toxigenic capsular type A strains associated with pneumonia represent distinct subpopulations of P. multocida that can be differentiated by their OMP-types. The association of capsular types A and D with strains of the same OMP-types, and the absence and presence of the toxA gene in strains of the same OMP-types, suggest that horizontal transfer of capsular biosynthesis and toxA genes has occurred between strains representing certain subpopulations of P. multocida. INTRODUCTIONPasteurella multocida is the aetiological agent of progressive atrophic rhinitis (PAR) of swine and is of considerable economic importance to the pig-rearing industry throughout the world (Chanter & Rutter, 1989). PAR is characterized by atrophy of the nasal turbinate bones which, in severe cases, can lead to facial distortion. P. multocida strains associated with PAR usually produce a 145-kDa dermonecrotic toxin, which is encoded by the toxA gene (Lax et al., 1990;Buys et al., 1990). This toxin induces osteolysis in the turbinate bones and plays an important role in the pathogenesis of PAR (Kamp & Kimman, 1988). Toxigenic strains associated with PAR are most frequently of capsular type D (Eamens et al., 1988;Foged et al., 1988;Gardner et al., 1994;Lariviere et al., 1992), although toxigenic isolates of capsular type A can also be involved in the disease (Fussing et al., 1999;Sakano et al., 1992). Non-toxigenic P. multocida strains are not usually associated with PAR and confirmation of toxin production is important for the diagnosis and control of the disea...

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“…The toxin is also mitogenic for the following established cell lines, Rat-1 [3], BALB/c 3T3, NIH 3T3, 3T6 and human fibroblasts [1]. The toxin has been cloned, sequenced and expressed in Escherichia co# [4][5][6][7][8][9]. PMT is encoded as a 146 kDa singlechain bacterial protein, which shares partial homology with the multinucleating toxins, cytotoxic necrotising factors types 1 and 2 (CNF-1, CNF-2), produced by some strains of E. coli [10,11].…”

Section: Introductionmentioning

confidence: 99%

The potent mitogen Pasteurella multocida toxin is highly resistant to proteolysis but becomes susceptible at lysosomal pH

Smyth¹,

Pickersgill²,

Lax³

1995

FEBS Letters

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The susceptibility of the potent mitogen Pasteurella multocida toxin (PMT) to various proteases was investigated. PMT at a toxin to protease molar ratio of 1 : 1 was resistant to 8 of the 11 proteases tested after one hour. With longer incubation, PMT remained resistant to 7 proteases, and this correlated with a retention of biological activity, indicating that PMT might not require proteolytic cleavage at least until it bound to a cell receptor. Previous evidence had suggested that PMT is processed in the cell via an endosome or lysosome. We have shown that PMT became susceptible to proteolysis when the pH was lowered to 5 or below. This supports the previous suggestion that PMT is processed via a low pH compartment in the cell.

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Sequence of the dermonecrotic toxin ofPasteurella multocida ssp. multocida

Cited by 42 publications

References 3 publications

Mammalian Target of Rapamycin Complex 1 (mTORC1) Plays a Role in Pasteurella multocida Toxin (PMT)-induced Protein Synthesis and Proliferation in Swiss 3T3 Cells

Mammalian Target of Rapamycin Complex 1 (mTORC1) Plays a Role in Pasteurella multocida Toxin (PMT)-induced Protein Synthesis and Proliferation in Swiss 3T3 Cells

Characterization and comparison of Pasteurella multocida strains associated with porcine pneumonia and atrophic rhinitis

The potent mitogen Pasteurella multocida toxin is highly resistant to proteolysis but becomes susceptible at lysosomal pH

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