Bordetella bronchiseptica dermonecrotizing toxin stimulates protein synthesis in an osteoblastic clone, MC3T3-E1 cells

Horiguchi, Yasuhiko

doi:10.1016/0378-1097(94)00169-3

Cited by 11 publications

(13 citation statements)

References 14 publications

(18 reference statements)

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“…In vitro studies have shown that purified DNT from B. bronchiseptica induces dramatic morphological changes, stimulates DNA replication, and impairs differentiation and proliferation in osteoblastic clone MC 3T3 cells (369,372). Recent evidence indicates that these effects are due to DNT-mediated activation of the small GTP-binding protein Rho (371), which results in tyrosine phosphorylation of focal adhesion kinase (p125 fak ) and paxillin (436).…”

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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“…B. bronchiseptica DNT produces dermonecrosis when injected intradermally into many animals including guinea pigs, mice, and rabbits and is lethal for mice when given intravenously (15). In cell cultures, DNT stimulates DNA and protein synthesis and assembly of actin stress fibers while inhibiting cell division, resulting in polynucleation of cells (19,20). It mediates these changes through modification and activation of the small GTP-binding protein, Rho (18).…”

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confidence: 99%

“…B. bronchiseptica DNT affects cultured cells; in particular, it inhibits alkaline phosphatase activity and reduces the type I collagen accumulation, both of which are linked to osteoblastic differentiation in an osteoblastic cell line, MC3T3-E1. Thus, impairment of the ability of osteoprogenitor cells to differentiate may result in decreased bone formation and may at least partially explain the nasal turbinate atrophy seen (16). DNT also stimulates DNA and protein synthesis in MC3T3-E1 cells but inhibits cell division, resulting in the formation of polynucleated cells (19,20).…”

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confidence: 99%

“…Thus, impairment of the ability of osteoprogenitor cells to differentiate may result in decreased bone formation and may at least partially explain the nasal turbinate atrophy seen (16). DNT also stimulates DNA and protein synthesis in MC3T3-E1 cells but inhibits cell division, resulting in the formation of polynucleated cells (19,20). DNT modifies members of the Rho family of small Gproteins either by deamidation or polyamination.…”

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confidence: 99%

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Role of the Dermonecrotic Toxin of Bordetella bronchiseptica in the Pathogenesis of Respiratory Disease in Swine

Brockmeier

Magyar

et al. 2002

Infect Immun

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Bordetella bronchiseptica is one of the etiologic agents causing atrophic rhinitis and pneumonia in swine. It produces several purported virulence factors, including the dermonecrotic toxin (DNT), which has been implicated in the turbinate atrophy seen in cases of atrophic rhinitis. The purpose of these experiments was to clarify the role of this toxin in respiratory disease by comparing the pathogenicity in swine of two isogenic dnt mutants to their virulent DNT ؉ parent strains. Two separate experiments were performed, one with each of the mutant-parent pairs. One-week-old cesarean-derived, colostrum-deprived pigs were inoculated intranasally with the parent strain, the dnt mutant strain, or phosphate-buffered saline. Weekly nasal washes were performed to monitor colonization of the nasal cavity, and the pigs were euthanized 4 weeks after inoculation to determine colonization of tissues and to examine the respiratory tract for pathology. There was evidence that colonization of the upper respiratory tract, but not the lower respiratory tract, was slightly greater for the parent strains than for the dnt mutants. Moderate turbinate atrophy and bronchopneumonia were found in most pigs given the parent strains, while there was no turbinate atrophy or pneumonia in pigs challenged with the dnt mutant strains. Therefore, production of DNT by B. bronchiseptica is necessary to produce the lesions of turbinate atrophy and bronchopneumonia in pigs infected with this organism.Bordetella bronchiseptica causes respiratory disease in many species (11). In particular, it is one of the etiologic agents of atrophic rhinitis and pneumonia in swine (10). The characteristic lesion of atrophic rhinitis is atrophy of the nasal turbinate bones. Microscopic lesions include mucosal infiltration by neutrophils, loss of cilia, metaplasia of the epithelium, and resorption of bone with replacement by fibrous tissue (9). Pulmonary lesions are characterized by infiltration of the airways with neutrophils, necrosis of the alveoli and blood vessels, hemorrhage, and, eventually, extensive fibrosis as the lesions become more chronic (8).B. bronchiseptica, like its close relative Bordetella pertussis, produces virulence factors which are regulated by a two-component sensory transduction system encoded by the bvg locus (3, 28). Some of the virulence factors which are positively regulated by bvg include adhesins such as filamentous hemagglutinin, pertactin, and fimbriae and the adenylate cyclase-hemolysin toxin and dermonecrotic toxin (DNT). B. bronchiseptica DNT produces dermonecrosis when injected intradermally into many animals including guinea pigs, mice, and rabbits and is lethal for mice when given intravenously (15). In cell cultures, DNT stimulates DNA and protein synthesis and assembly of actin stress fibers while inhibiting cell division, resulting in polynucleation of cells (19,20). It mediates these changes through modification and activation of the small GTP-binding protein, Rho (18). DNT has been implicated in the nasal turbinate atrop...

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“…B. bronchiseptica DNT is considered to be responsible for turbinate atrophy in swine atrophic rhinitis (4,6,9). The turbinate atrophy caused by DNT likely results from a deficiency of osteoblastic differentiation in bone tissues (9,11).…”

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Identification of a Receptor-Binding Domain of Bordetella Dermonecrotic Toxin

et al. 2002

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Dermonecrotic toxin (DNT), commonly produced by Bordetella pertussis, Bordetella bronchiseptica, and Bordetella parapertussis, exerts lethal, dermonecrotic, and splenoatrophic activities in a variety of experimental animals (2,3,7,8,12,19). B. bronchiseptica DNT is considered to be responsible for turbinate atrophy in swine atrophic rhinitis (4, 6, 9). The turbinate atrophy caused by DNT likely results from a deficiency of osteoblastic differentiation in bone tissues (9, 11). DNT also alters cell morphology, stimulating the anomalous reorganization of actin stress fibers and focal adhesions, which is elaborately regulated by the small GTPase Rho (5, 10). The small GTPases function as a molecular switch regulating various cell functions besides the reorganization of actin cytoskeletons by changing between the GDP-bound inactive and the GTPbound active forms. The GDP-bound GTPases in resting cells exchange GDP for GTP in response to various stimulations, transduce the signals downstream by interacting with effector proteins, and thereafter revert to the GDP-bound inactive form by hydrolyzing the bound GTP. Our research group recently demonstrated that DNT was a transglutaminase catalyzing deamidation or polyamination at Gln63 of Rho and the corresponding Gln residues of the other members of the Rho family, Rac and Cdc42 (5, 18). The deamidation and polyamination result in a reduction of the GTP hydrolyzing activity. In addition, the polyaminated Rho comes to interact with a downstream effector, ROCK, in a GTP-independent manner (17). Thus, these modifications render the intracellular GTPases constitutively active, which probably mediates various effects of DNT on target cells.DNT is a single-chain polypeptide which consists of 1,464 amino acids with a calculated molecular mass of 160,602 (13). Previously, we localized the catalytic domain of DNT to the C-terminal region from Ile 1176 to the C-terminal end. We also found that the N-terminal fragment spanning Met 1 to Pro 531 of DNT competitively blocked the intoxication of cells by the full-length DNT (13), implying that this fragment retains the receptor-binding or internalizing property. In the present study, we attempted to define the N-terminal receptor-binding region of DNT by using a series of toxin mutants with various lengths and a monoclonal antibody (MAb) that neutralizes the toxin. The results presented here indicate that DNT binds to the cells through the N-terminal region consisting of 54 amino acids, in which the MAb recognized the region including Arg 44 . MATERIALS AND METHODSMaterials. DNT was purified from B. bronchiseptica S798 as described previously (8). The numbering of the amino acids of DNT was based on the sequence available from the DDBJ/EMBL/GenBank databases under accession no. AB020025. C3 exoenzyme was provided by S. Kozaki, University of Osaka Prefecture, Osaka, Japan. MC3T3-E1 cells were cultured at 37°C in ␣-minimum essential medium (␣-MEM; Gibco Laboratories, Grand Island, N.Y.) supplemented with 10% fetal calf serum under 5% CO 2 ...

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Bordetella bronchiseptica dermonecrotizing toxin stimulates protein synthesis in an osteoblastic clone, MC3T3-E1 cells

Cited by 11 publications

References 14 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

Role of the Dermonecrotic Toxin of Bordetella bronchiseptica in the Pathogenesis of Respiratory Disease in Swine

Identification of a Receptor-Binding Domain of Bordetella Dermonecrotic Toxin

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