Lienotoxicity Of Bordetella Pertussis In Mice

Iida, Tsuyoshi; Okonogi, Takashi

doi:10.1099/00222615-4-1-51

Cited by 36 publications

(16 citation statements)

References 11 publications

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“…Although initially misidentified as an endotoxin, DNT was one of the first B. pertussis virulence factors to be described (62). This heat-labile toxin induces localized necrotic lesions in mice and other laboratory animals when injected intradermally and is lethal for mice at low doses when administered intravenously (62,377,470,609). The DNTs of B. pertussis, B. bronchiseptica, and B. parapertussis hu are nearly identical (ϳ99% amino acid identity) cytoplasmic, single polypeptide chains of about 160 kDa (183,370,580,846).…”

Section: Virulence Determinantsmentioning

confidence: 99%

Molecular Pathogenesis, Epidemiology, and Clinical Manifestations of Respiratory Infections Due toBordetella pertussisand OtherBordetellaSubspecies

2005

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Bordetella respiratory infections are common in people (B. pertussis) and in animals (B. bronchiseptica). During the last two decades, much has been learned about the virulence determinants, pathogenesis, and immunity of Bordetella. Clinically, the full spectrum of disease due to B. pertussis infection is now understood, and infections in adolescents and adults are recognized as the reservoir for cyclic outbreaks of disease. DTaP vaccines, which are less reactogenic than DTP vaccines, are now in general use in many developed countries, and it is expected that the expansion of their use to adolescents and adults will have a significant impact on reducing pertussis and perhaps decrease the circulation of B. pertussis. Future studies should seek to determine the cause of the unique cough which is associated with Bordetella respiratory infections. It is also hoped that data gathered from molecular Bordetella research will lead to a new generation of DTaP vaccines which provide greater efficacy than is provided by today's vaccines

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Section: Virulence Determinantsmentioning

confidence: 99%

Molecular Pathogenesis, Epidemiology, and Clinical Manifestations of Respiratory Infections Due toBordetella pertussisand OtherBordetellaSubspecies

2005

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“…Dermonecrotizing toxin (DNT) produced by bacteria of the Bordetella species has lethal, dermonecrotic, and splenoatrophic activities (1)(2)(3). DNT is considered to be one of the virulence factors responsible for turbinate atrophy in swine atrophic rhinitis and has been suggested to damage bone tissues in turbinates (4,5).…”

mentioning

confidence: 99%

Bordetella bronchiseptica dermonecrotizing toxin induces reorganization of actin stress fibers through deamidation of Gln-63 of the GTP-binding protein Rho

Horiguchi

Inoue

Masuda

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

109

116

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Bordetella dermonecrotizing toxin causes assembly of actin stress fibers and focal adhesions in some cultured cells and induces mobility shifts of the small GTP-binding protein Rho on electrophoresis. We attempted to clarify the molecular basis of the toxin action on Rho. Analysis of the amino acid sequence of toxin-treated RhoA revealed the deamidation of Gln-63 to Glu. The substitution of Glu for Gln-63 of RhoA by site-directed mutagenesis caused a mobility shift on electrophoresis, which was indistinguishable from that of the toxintreated RhoA. Neither mutant RhoA-bearing Glu-63 nor toxintreated RhoA significantly differed from untreated wild type RhoA in guanosine 5-[␥-thio]triphosphate binding activity but both showed a 10-fold reduction in GTP hydrolysis activity relative to untreated RhoA. C3H10T1͞2 cells transfected with cDNA of the mutant RhoA bearing Glu-63 showed extensive formation of actin stress fibers similar to the toxin-treated cells. These results indicate that the toxin catalyzes deamidation of Gln-63 of Rho and renders it constitutively active, leading to formation of actin stress fibers.Dermonecrotizing toxin (DNT) produced by bacteria of the Bordetella species has lethal, dermonecrotic, and splenoatrophic activities (1-3). DNT is considered to be one of the virulence factors responsible for turbinate atrophy in swine atrophic rhinitis and has been suggested to damage bone tissues in turbinates (4, 5). Using osteoblast-like MC3T3-E1 cells, we demonstrated that DNT changes cell morphology and inhibits the differentiation into osteoblasts (6). The morphological changes in DNT-treated cells were accompanied by the assembly of actin stress fibers and focal adhesions, indicating anomalous activation of the small GTP-binding protein Rho (7). It was also found that Rho in the lysate from DNT-treated cells showed shifts in its electrophoretic mobility. Similar mobility shifts of Rho were observed by in vitro treatment of recombinant Rho with DNT. These results indicate that DNT covalently modifies and activates Rho, leading to the assembly of actin stress fibers and focal adhesions. However, the nature of the DNT-induced modification of Rho, which relates to its activation remains unknown.Here, we show that DNT catalyzes the deamidation of Gln-63 of RhoA and converts it into Glu. We conclude that the deamidated RhoA bearing Glu-63 becomes constitutively active and stimulates the formation of actin stress fibers in DNT-treated cells.

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“…Phase I organism of Bordetella species produce a biologically similar heat-labile toxin (HLT) which is dermonecrotizing, lethal and lienotoxic when injected into mice, rabbits or guinea pigs (3,7,8,12,14,20,30). Since its discovery by Bordet and Gengou (1), numerous attempts have been made to purify and characterize the HLT from B. pertussis, but not from other Bordetella organisms.…”

mentioning

confidence: 99%

“…Since its discovery by Bordet and Gengou (1), numerous attempts have been made to purify and characterize the HLT from B. pertussis, but not from other Bordetella organisms. However, no definitive results are yet available, because of its characteristic instability and poor or unreliable recovery from the column-packing materials (12,20,22,24,28,30). Therefore, the exact mode of action of the purified HLT remains obscure.…”

mentioning

confidence: 99%

Purification and Characterization of Heat‐Labile Toxin from Bordetella bronchiseptica

Endoh

Amitani

Nakase

1986

Microbiology and Immunology

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The heat-labile toxin (HLT) of Bordetella bronchiseptica was purified successively from sonic extracts of phase I organisms grown in Stainer-Scholte medium, by partition in hydrophobic interaction, sucrose density gradient centrifugation, gel filtration through Sepharose 4B and 6B, isoelectric precipitation and isoelectric focusing. The purified HLT was homogeneous by disc polyacrylamide gel electrophoresis and the gel diffusion-test, and free of detectable hemagglutinin and endotoxin activity. A 386-fold purification over the crude extract was obtained at a yield of about 28%, and a minimum dose of 0.9 ng was dermonecrotizing with a lesion 5 mm in diameter in guinea pigs and induced splenoatrophy. The mouse LD50 was 200 ng (intraperitoneal) or 70 ng (intravenous). The HLT was found to be a simple protein with an isoelectric point of pI 6.9. It has a molecular weight of 102,000 estimated by Sepharose 6B gel filtration and was found to consist of two different types of polypeptide by SDS-polyacrylamide gel electrophoresis, their molecular weights being 30,000 and 20,000. Amino acid analysis showed 15 common amino acid residues, and methionine, cysteine and tryptophan were undetectable. The HLT crystallized by methylpentanediol showed a block form. The HLT was inactivated at 56 C when heated for 10 min, and at above pH 9 and below pH 4.

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Lienotoxicity Of Bordetella Pertussis In Mice

Cited by 36 publications

References 11 publications

Molecular Pathogenesis, Epidemiology, and Clinical Manifestations of Respiratory Infections Due toBordetella pertussisand OtherBordetellaSubspecies

Molecular Pathogenesis, Epidemiology, and Clinical Manifestations of Respiratory Infections Due toBordetella pertussisand OtherBordetellaSubspecies

Bordetella bronchiseptica dermonecrotizing toxin induces reorganization of actin stress fibers through deamidation of Gln-63 of the GTP-binding protein Rho

Purification and Characterization of Heat‐Labile Toxin from Bordetella bronchiseptica

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