Atrophic Rhinitis

Tibor Magyar; Alistair J. Lax

doi:10.1128/9781555817947.ch10

Chapter 10 : Atrophic Rhinitis

Authors: Tibor Magyar¹, Alistair J. Lax²

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Affiliations: 1: Veterinary Medical Research Institute, Hungarian Academy of Sciences, H-1143 Budapest, Hungary; 2: Oral Microbiology, Guy's King's and St. Thomas' Dental Institute, King's College London, London SE1 9RT, United Kingdom

Content Type: Monograph

Publication Year: 2002

Category: Clinical Microbiology

Book DOI: 10.1128/9781555817947

Chapter DOI: 10.1128/9781555817947.ch10

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Abstract:

Atrophic rhinitis is a contagious respiratory disease of pigs that is highly prevalent throughout the world where modern pig husbandry is practiced. Several agents were suspected to be etiological agents in the early studies. These included bacteria (Pseudomonas, Actinomyces, Sphaerophorus, Corynebacterium, or Mycoplasma), a virus (cytomegalovirus), and trichomonads. However, only certain defined strains of Bordetella bronchiseptica and Pasteurella multocida proved to be able to constantly reproduce marked turbinate atrophy, the most characteristic lesion of atrophic rhinitis. A productive P. multocida infection needs predisposing factors among which B. bronchiseptica preinfection is the most commonly recognized one. This interaction between the two pathogens classifies atrophic rhinitis as a member of the family of polymicrobial infections, and the disease are reviewed with special attention to this aspect. The dominant pathological lesion of atrophic rhinitis is an atrophy of the nasal turbinate bones as assessed by transverse section of the nasal cavity at the level of the first/second upper premolar teeth where the dorsal and ventral conchae are maximally developed in the normal pig. Atrophic rhinitis is thought to reduce growth rates, which makes it an economically important disease for pig producers. Vaccination is widely used to try to reduce the prevalence of atrophic rhinitis in herds affected by the disease. The specific synergistic interactions between B. bronchiseptica and P. multocida support the notion that it is a genuine polymicrobial disease, which in addition may serve as a useful model system for more complex mixed infections.

Citation: Magyar T, Lax A. 2002. Atrophic Rhinitis, p 169-198. In Brogden K, Guthmiller J (ed), Polymicrobial Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817947.ch10

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Atrophic Rhinitis

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Citation: Magyar T, Lax A. 2002. Atrophic Rhinitis, p 169-198. In Brogden K, Guthmiller J (ed), Polymicrobial Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817947.ch10

/content/10.1128/9781555817947.chap10.fig10-1

FIGURE 1

Cross-sections of snouts of 6-week-old pigs. (a) Uninfected pig showing normal anatomy of nasal structures. (b) Pig after infection with B. bronchiseptica and toxigenic P. multocida. The left dorsal turbinate is absent, and only a band of connective tissue remains from the left ventral turbinate. The right dorsal turbinate is slightly shrunken, and both scrolls of the right ventral turbinate show moderate atrophy. (c) Pig after infection with B. bronchiseptica and toxigenic P. multocida. There is complete absence of all turbinate structures accompanied with slight lateral deviation of the nasal septum.

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10.1128/9781555817947/fig10-1.gif

FIGURE 1

Citation: Magyar T, Lax A. 2002. Atrophic Rhinitis, p 169-198. In Brogden K, Guthmiller J (ed), Polymicrobial Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817947.ch10

/content/10.1128/9781555817947.chap10.fig10-2

FIGURE 2

Diagram of some of the signal transduction pathways affected by the dermonecrotic (DNT) and adenylate cyclase (Ad cyclase) toxins from B. bronchiseptica and by the P. multocida toxin (PMT). Targets modified by the toxins are shown by open arrows. Direct interaction between molecules is shown by solid arrows, and interactions where the intervening components are either not shown or not known are indicated by dotted arrows. Abbreviations: GPCR, G-protein-coupled receptor; Gq α and G12/13 α, the alpha subunits of the respective heterotrimeric G proteins; PKA, protein kinase A; cAMP, cyclic AMP; MEK, MAP kinase/extracellular signal-regulated kinase kinase; ERK, extracellular signal-regulated kinase.

10.1128/9781555817947/fig10-2_thmb.gif

10.1128/9781555817947/fig10-2.gif

FIGURE 2

Citation: Magyar T, Lax A. 2002. Atrophic Rhinitis, p 169-198. In Brogden K, Guthmiller J (ed), Polymicrobial Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817947.ch10

/content/10.1128/9781555817947.chap10.fig10-3

FIGURE 3

Diagram of some of the potential virulence determinants regulated by the bvg genes in Bordetella species. Abbreviations: bvg, Bordetella virulence gene; vrg, vir (bvg)- repressed gene; FHA, filamentous hemagglutinin. Tibor Magyar, Veterinary Medical Research Institute, Hungarian Academy of Sciences, H-1143 Budapest, Hungary. Alistair J. Lax, Oral Microbiology, Guy's King's and St. Thomas' Dental Institute, King's College London, London SE1 9RT, United Kingdom.

10.1128/9781555817947/fig10-3_thmb.gif

10.1128/9781555817947/fig10-3.gif

FIGURE 3

Citation: Magyar T, Lax A. 2002. Atrophic Rhinitis, p 169-198. In Brogden K, Guthmiller J (ed), Polymicrobial Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817947.ch10

References

/content/book/10.1128/9781555817947.chap10

1. Ackermann, M. R.,, D. A. Adams,, L. L. Gerken,, M. J. Beckman,, and R. B. Rimler. 1993. Purified Pasteurella multocida protein toxin reduces acid phosphatase-positive osteoclasts in the ventral nasal concha of gnotobiotic pigs. Calcif. Tissue Int. 52: 455– 459.

2. Ackermann, M. R.,, R. B. Rimler,, and J. R. Thurston. 1991. Experimental model of atrophic rhinitis in gnotobiotic pigs. Infect. Immun. 59: 3626– 3629.

3. Akerley, B. J.,, D. M. Monack,, S. Falkow,, and J. F. Miller. 1992. The bvgAS locus negatively controls motility and synthesis of flagella in Bordetella bronchiseptica. J. Bacteriol. 174: 980– 990.

4. Alexander, T. J. L.,, K. Thornton,, G. Boon,, R. J. Lysons,, and A. F. Gush. 1980. Medicated early weaning to obtain pigs free from pathogens endemic in the herd of origin. Vet. Rec. 106: 114– 119.

5. Andreasen, M.,, P. Baekbo,, and J. P. Nielsen. 2000. Lack of effect of aerial ammonia on atrophic rhinitis and pneumonia induced by Mycoplasma hyopneumoniae and toxigenic Pasteurella multocida. J. Vet. Med. Ser. B 47: 161– 171.

6. Bäckström, L.,, D. C. Hoefling,, A. C. Morkoc,, and R. P. Cowart. 1985. Effect of atrophic rhinitis on growth rate in Illinois swine herds. J. Am. Vet. Med. Assoc. 187: 712– 715.

7. Banemann, A.,, and R. Gross. 1997. Phase variation affects long-term survival of Bordetella bronchiseptica in professional phagocytes. Infect. Immun. 65: 3469– 3473.

8. Beachey, E. H. 1981. Bacterial adherence: adhesin- receptor interactions mediating the attachment of bacteria to mucosal surfaces. J. Infect. Dis. 143: 325– 345.

9. Betsou, F.,, O. Sismeiro,, A. Danchin,, and N. Guiso. 1995. Cloning and sequence of the Bordetella bronchiseptica adenylate cyclasehemolysin- encoding gene. Gene 162: 165– 166.

10. Bjorge, J. D.,, A. Jakymiw,, and D. J. Fujita. 2000. Selected glimpses into the activation and function of Src kinase. Oncogene 19: 5620– 5635.

11. Bock, A.,, and R. Gross. 2001. The BvgAS two-component system of Bordetella spp.: a versatile modulator of virulence gene expression. Int. J. Med. Microbiol. 291: 119– 130.

12. Bordet, J.,, and O. Gengou. 1909. Le microbe de la coqueluche. Ann. Inst. Pasteur 20: 731– 741.

13. Boschwitz, J. S.,, H. G. J. van der Heide,, F. R. Mooi,, and D. A. Relman. 1997. Bordetella bronchiseptica expresses the fimbrial structural subunit gene fimA. J. Bacteriol. 179: 7882– 7885.

14. Boursaux-Eude, C.,, and N. Guiso. 2000. Polymorphism of repeated regions of pertactin in Bordetella pertussis, Bordetella parapertussis and Bordetella bronchiseptica. Infect. Immun. 68: 4815– 4817.

15. Braend, M.,, and J. L. Flatla. 1954. Rhinitis infectiosa atroficans hos gris. Nord. Vetmed. 6: 81– 122.

16. Brassine, M.,, A. Dewaele,, and M. Gouffaux. 1976. Intranasal infection with Bordetella bronchiseptica in gnotobiotic piglets. Res. Vet. Sci. 20: 162– 166.

17. Brennan, M. J.,, Z. M. Li,, J. L. Cowell,, M. E. Bisher,, A. C. Steven,, P. Novotny,, and C. R. Manclark. 1988. Identification of a 69-kilodalton nonfimbrial protein as an agglutinogen of Bordetella pertussis. Infect. Immun. 56: 3189– 3195.

18. Brockmeier, S. L. 1999. Early colonization of the rat upper respiratory tract by temperature modulated Bordetella bronchiseptica. FEMS Microbiol. Lett. 174: 225– 229.

19. Brockmeier, S. L.,, and K. B. Register. 2000. Effect of temperature modulation and bvg mutation of Bordetella bronchiseptica on adhesion, intracellular survival and cytotoxicity for swine alveolar macrophages. Vet. Microbiol. 73: 1– 12.

20. Brown, W. R.,, L. Krook,, and W. G. Pond. 1966. Atrophic rhinitis in swine. Etiology, pathogenesis and prophylaxis. Cornell Vet. 56(Suppl. 1): 1– 108.

21. Burns, E. H., Jr.,, J. M. Norman,, M. D. Hatcher,, and D. A. Bemis. 1993. Fimbriae and determination of host species specificity of Bordetella bronchiseptica. J. Clin. Microbiol. 31: 1838– 1844.

22. Busch, C.,, J. Orth,, N. Djouder,, and K. Aktories. 2001. Biological activity of a C-terminal fragment of Pasteurella multocida toxin. Infect. Immun. 69: 3628– 3634.

23. Cantrell, D. A. 2001. Phosphoinositide 3-kinase signalling pathways. J. Cell Sci. 114: 1439– 1445.

24. Chanter, N.,, and J. M. Rutter. 1990. Colonisation by Pasteurella multocida in atrophic rhinitis of pigs and immunity to the osteolytic toxin. Vet. Microbiol. 25: 253– 265.

25. Chanter, N.,, J. M. Rutter,, and A. MacKenzie. 1986. Partial purification of an osteolytic toxin from Pasteurella multocida. J. Gen. Microbiol. 132: 1089– 1097.

26. Chanter, N.,, T. Magyar,, and J. M. Rutter. 1989. Interactions between Bordetella bronchiseptica and toxigenic Pasteurella multocida in atrophic rhinitis of pigs. Res. Vet. Sci. 47: 48– 53.

27. Charles, I. G.,, G. Dougan,, D. Pickard,, S. Chatfield,, M. Smith,, P. Novotny,, P. Morrissey,, and N. F. Fairweather. 1989. Molecular cloning and characterization of protective outer membrane protein P.69 from Bordetella pertussis. Proc. Natl. Acad. Sci. USA 86: 3554– 3558.

28. Cheville, N. F.,, R. B. Rimler,, and J. Thurston. 1988. A toxin from Pasteurella multocida type D causes acute hepatic necrosis in pigs. Vet. Pathol. 25: 518– 520.

29. Chung, W. B.,, M. T. Collins,, and L. R. Bäckström. 1990. Adherence of Bordetella bronchiseptica and Pasteurella multocida to swine nasal ciliated epithelial cells in vitro. APMIS 98: 453– 461.

30. Collings, L. A.,, and J. M. Rutter. 1985. Virulence of Bordetella bronchiseptica in the porcine respiratory tract. J. Med. Microbiol. 19: 247.

31. Confer, D. L.,, and J. W. Eaton. 1982. Phagocyte impotence caused by an invasive bacterial adenylate cyclase. Science 217: 948– 950.

32. Cookson, B. T.,, and W. E. Goldman. 1987. Tracheal cytotoxin: a conserved virulence determinant of all Bordetella species. J. Cell. Biochem. 11B( Suppl.): 124.

33. Cookson, B. T.,, H.-L. Cho,, L. A. Herwaldt,, and W. E. Goldman. 1989. Biological activities and chemical composition of purified tracheal cytotoxin of Bordetella pertussis. Infect. Immun. 57: 2223– 2229.

34. Cornelis, G. R.,, and F. Van Gijsegem. 2000. Assembly and function of type III secretory systems. Annu. Rev. Microbiol. 54: 735– 774.

35. Cotter, P. A.,, and J. F. Miller. 1994. BvgAS-mediated signal transduction: analysis of phaselocked regulatory mutants of Bordetella bronchiseptica in a rabbit model. Infect. Immun. 62: 3381– 3390.

36. Cotter, P. A.,, and J. F. Miller. 2000. Genetic analysis of the Bordetella infectious cycle. Immunopharmacology 48: 253– 255.

37. Cotter, P. A.,, M. H. Yuk,, S. Mattoo,, B. J. Akerley,, J. S. Boschwitz,, D. A. Relman,, and J. F. Miller. 1998. Filamentous hemagglutinin of Bordetella bronchiseptica is required for efficient establishment of tracheal colonization. Infect. Immun. 66: 5921– 5929.

38. Cowell, J. L.,, E. L. Hewlett,, and D. R. Manclark. 1979. Intracellular localization of the dermonecrotic toxin of Bordetella pertussis. Infect. Immun. 25: 896– 901.

39. Cross, R. F.,, and R. M. Claflin. 1962. Bordetella bronchiseptica induced porcine atrophic rhinitis. J. Am. Vet. Med. Assoc. 141: 1467– 1468.

40. Cundell, D. R.,, K. Kanthakumar,, G. W. Taylor,, W. E. Goldman,, T. Flak,, P. J. Cole,, and R. Wilson. 1994. Effect of tracheal cytotoxin from Bordetella pertussis on human neutrophil function in vitro. Infect. Immun. 62: 639– 643.

41. de Jong, M. F., 1983. Atrophic rhinitis caused by intranasal or intramuscular administration of broth-culture and broth-culture filtrates containing AR toxin of Pasteurella multocida, p. 136– 146. In K. B. Pedersen, and J. C. Nielsen (ed.), Atrophic Rhinitis in Pigs. Report EUR 8643 EN. Commission of the European Communities, Luxembourg, Luxembourg.

42. de Jong, M. F., 1999. Progressive and nonprogressive atrophic rhinitis, p. 355– 384. In B. E. Straw,, S. D’Allaire,, W. L. Mengeling,, and D. J. Taylor (ed.), Diseases of Swine, 8th ed. Iowa State University Press, Ames..

43. de Jong, M. F.,, and J. P. Nielsen. 1990. Definition of progressive atrophic rhinitis. Vet. Rec. 27: 93.

44. Dominick, M. A.,, and R. B. Rimler. 1986. Turbinate atrophy in gnotobiotic pigs intranasally inoculated with protein toxin isolated from type D Pasteurella multocida. Am. J. Vet. Res. 47: 1532– 1536.

45. Dugal, F.,, M. Belanger,, and M. Jacques. 1992. Enhanced adherence of Pasteurella multocida to porcine tracheal rings preinfected with Bordetella bronchiseptica. Can. J. Vet. Res. 56: 260– 264.

46. Duncan, J. R.,, R. K. Ross,, W. P. Switzer,, and R. K. Ramsey. 1966. Pathology of experimental Bordetella bronchiseptica infection in swine: atrophic rhinitis. Am. J. Vet. Res. 27: 457– 466.

47. Éliás, B.,, and D. Hámori. 1975. Adatok a sertés torzító orrgyulladásának kóroktanához. V. A genetikai tényezók szerepe. Magy. Állatorv. Lapja 30: 535– 539.

48. Endoh, M.,, T. Takezawa,, and Y. Nakase. 1980. Adenylate cyclase activity of Bordetella organisms. Microbiol. Immunol. 24: 95– 104.

49. Essler, M.,, K. Hermann,, M. Amano,, K. Kaibuchi,, J. Heesemann,, P. C. Weber,, and M. Aelfelbacher. 1998. Pasteurella multocida toxin increases endothelial permeability via Rho kinase and myosin light chain phosphatase. J. Immunol. 161: 5640– 5646.

50. Felix, R.,, H. Fleisch,, and P. L. Frandsen. 1992. Effect of Pasteurella multocida toxin on bone resorption in vitro. Infect. Immun. 60: 4984– 4988.

51. Foged, N. T.,, J. P. Nielsen,, and S. E. Jorsal. 1989. Protection against progressive atrophic rhinitis by vaccination with Pasteurella multocida toxin purified by monoclonal antibodies. Vet. Rec. 125: 7– 11.

52. Forde, C. B.,, R. Parton,, and J. G. Coote. 1998. Bioluminescence as a reporter of intracellular survival of Bordetella bronchiseptica in murine phagocytes. Infect. Immun. 66: 3198– 3207.

53. Forde, C. B.,, X. Shi,, J. Li,, and M. Roberts. 1999. Bordetella bronchiseptica-mediated cytotoxicity to macrophages is dependent on bvg-regulated factors, including pertactin. Infect. Immun. 67: 5972– 5978.

54. Franque, L. W. 1830. Was ist die Schnüffelkrankheit der Schweine? Dtsch. Z. Gesamte Tierheilkd. 1: 75– 77.

55. Frymus, T.,, M. M. Wittenbrink,, and K. Petzold. 1986. Failure to demonstrate adherence of Pasteurella multocida involved in atrophic rhinitis to swine nasal epithelial cells. J. Vet. Med. Ser. B 33: 140– 144.

56. Fuller, T. E.,, M. J. Kennedy,, and D. E. Lowery. 2000. Identification of Pasteurella multocida virulence genes in a septicemic mouse model using signature-tagged mutagenesis. Microb. Pathog. 29: 25– 38.

57. Gagné, S.,, and B. Martineau-Doizé. 1993. Nasal epithelial changes induced in piglets by acetic acid and by B. bronchiseptica. J. Comp. Pathol. 109: 71– 81.

58. Giardina, P. C.,, L. A. Foster,, J. M. Musser,, B. J. Akerley,, J. F. Miller,, and D. W. Dyer. 1995. bvg repression of alcaligin synthesis in Bordetella bronchiseptica is associated with phylogenetic lineage. J. Bacteriol. 177: 6058– 6063.

59. Giles, C. J. 1981. Atrophic Rhinitis of Pigs: Studies on the Naturally-Occurring and Experimental Disease in England, with Particular Reference to Bordetella bronchiseptica Infection. Ph.D. thesis. University of London, London, United Kingdom.

60. Giles, C. J.,, and I. M. Smith. 1983. Vaccination of pigs with Bordetella bronchiseptica. Vet. Bull. 53: 327– 338.

61. Giles, C. J.,, I. M. Smith,, A. J. Baskerville,, and E. Brothwell. 1980. Clinical, bacteriological and epidemiological observation on infectious atrophic rhinitis of pigs in Southern England. Vet. Rec. 106: 25– 28.

62. Glaser, P.,, D. Ladant,, O. Sezer,, F. Pichot,, A. Ullmann,, and A. Danchin. 1988a. The calmodulin-sensitive adenylate cyclase of Bordetella pertussis: cloning and expression in Escherichia coli. Mol. Microbiol. 2: 19– 30.

63. Glaser, P.,, H. Sakamoto,, J. Bellalou,, A. Ullmann,, and A. Danchin. 1988b. Secretion of cyclolysin, the calmodulin-sensitive adenylate cyclase-haemolysin bifunctional protein of Bordetella pertussis. EMBO J. 7: 3997– 4004.

64. Goldman, W. E.,, and B. T. Cookson. 1988. Structure and functions of the Bordetella tracheal cytotoxin. Tokai J. Exp. Clin. Med. 13(Suppl.): 187– 191.

65. Goldman, W. E.,, D. G. Klapper,, and J. B. Baseman. 1982. Detection, isolation, and analysis of a released Bordetella pertussis product toxic to cultured tracheal cells. Infect. Immun. 36: 782– 794.

66. Goodnow, R. A. 1980. Biology of Bordetella bronchiseptica. Microbiol. Rev. 44: 722– 738.

67. Goodwin, M. S. M.,, and A. A. Weiss. 1990. Adenylate cyclase is critical for colonization and pertussis toxin is critical for lethal infection by Bordetella pertussis in infant mice. Infect. Immun. 58: 3445– 3447.

68. Gueirard, P.,, A. Druilhe,, M. Pretolani,, and N. Guiso. 1998. Role of adenylate cyclasehemolysin in alveolar macrophage apoptosis during Bordetella pertussis infection in vivo. Infect. Immun. 66: 1718– 1725.

69. Guiso, N.,, M. Szatanik,, and M. Rocancourt. 1989. Protective activity of Bordetella adenylate cyclase-hemolysin against bacterial colonization. Microb. Pathog. 11: 423– 431.

70. Gwaltney, S. M.,, R. J. S. Galvin,, K. B. Register,, R. B. Rimler,, and M. R. Ackermann. 1997. Effects of Pasteurella multocida toxin on porcine bone marrow cell differentiation into osteoclasts and osteoblasts. Vet. Pathol. 34: 421– 430.

71. Gwatkin, R.,, L. Ozenis,, and J. L. Byrne. 1953. Rhinitis of swine. VII. Production of lesions in pigs and rabbits with a pure culture of Pasteurella multocida. Can. J. Comp. Med. Vet. Sci. 17: 215– 217.

72. Hackett, M.,, L. Guo,, J. Shabanowitz,, D. F. Hunt,, and E. L. Hewett. 1994. Internal lysine palmitoylation in adenylate cyclase toxin from Bordetella pertussis. Science 266: 433– 435.

73. Hamilton, T. D. C.,, J. M. Roe,, and A. J. F. Webster. 1996. Synergistic role of gaseous ammonia in etiology of Pasteurella multocida-induced atrophic rhinitis in swine. J. Clin. Microbiol. 34: 2185– 2190.

74. Hamilton, T. D. C.,, J. M. Roe,, C. M. Hayes,, and A. J. F. Webster. 1998. Effects of ammonia inhalation and acetic acid pretreatment on colonization kinetics of toxigenic Pasteurella multocida within upper respiratory tracts of swine. J. Clin. Microbiol. 36: 1260– 1265.

75. Hamilton, T. D. C.,, J. M. Roe,, C. M. Hayes,, P. Jones,, G. R. Pearson,, and A. J. F. Webster. 1999. Contributory and exacerbating roles of gaseous ammonia and organic dust in the etiology of atrophic rhinitis. Clin. Diagn. Lab. Immunol. 6: 199– 203.

76. Hanada, M.,, K. Shimoda,, S. Tomita,, Y. Nakase,, and Y. Nishiyama. 1979. Production of lesions similar to naturally occurring swine atrophic rhinitis by cell-free sonicated extract of Bordetella bronchiseptica. Jpn. J. Vet. Sci. 41: 1– 8.

77. Hannan, P. C.,, P. J. O’Hanlon,, and N. H. Rogers. 1989. In vitro evaluation of various quinolone antibacterial agents against veterinary mycoplasmas and porcine respiratory bacterial pathogens. Res. Vet. Sci. 46: 202– 211.

78. Hanski, E.,, and Z. Farfel. 1985. Bordetella pertussis invasive adenylate cyclase. J. Biol. Chem. 260: 5526– 5532.

79. Harris, D. L.,, and W. P. Switzer. 1968. Turbinate atrophy in young pigs exposed to Bordetella bronchiseptica, Pasteurella multocida and combined inoculum. Am. J. Vet. Res. 29: 777– 785.

80. Harvill, E. T.,, P. A. Cotter,, M. H. Yuk,, and J. F. Miller. 1999. Probing the function of Bordetella bronchiseptica adenylate cyclase toxin by manipulating host immunity. Infect. Immun. 67: 1493– 1500.

81. Heiss, L. N.,, J. J. Lancaster,, J. A. Corbett,, and W. E. Goldman. 1994. Epithelial autotoxicity of nitric oxide: role in the respiratory cytopathology of pertussis. Proc. Natl. Acad. Sci. USA 91: 267– 270.

82. Heiss, L. N.,, S. A. Moser,, E. R. Unanue,, and W. E. Goldman. 1993. Interleukin-1 is linked to the respiratory epithelial cytopathology of pertussis. Infect. Immun. 61: 3123– 3128.

83. Hewlett, E.,, and J. Wolff. 1976. Soluble adenylate cyclase from the culture medium of Bordetella pertussis: purification and characterization. J. Bacteriol. 127: 890– 898.

84. Hewlett, E. L.,, C. R. Manclark,, and J. Wolff. 1977. Adenylate cyclase in Bordetella pertussis vaccines. J. Infect. Dis. 136: 5216– 5219.

85. Hewlett, E. L.,, M. A. Urban,, C. R. Manclark,, and J. Wolff. 1976. Extracytoplasmic adenylate cyclase of Bordetella pertussis. Proc. Natl. Acad. Sci. USA 73: 1926– 1930.

86. Higgins, T. E.,, A. C. Murphy,, J. M. Staddon,, A. J. Lax,, and E. Rozengurt. 1992. Pasteurella multocida toxin is a potent inducer of anchorage- independent cell growth. Proc. Natl. Acad. Sci. USA 89: 4240– 4244.

87. Horiguchi, Y.,, H. Matsuda,, H. Koyama,, T. Nakai,, and K. Kume. 1992. Bordetella bronchiseptica dermonecrotizing toxin suppressed in vivo antibody responses in mice. FEMS Microbiol. Lett. 90: 229– 234.

88. Horiguchi, Y.,, N. Inoue,, M. Masuda,, T. Kashimoto,, J. Katahira,, N. Sugimoto,, and M. Matsuda. 1997. Bordetella bronchiseptica dermonecrotizing toxin induces reorganization of actin stress fibers through deamidation of Gln-63 of the GTP-binding protein Rho. Proc. Natl. Acad. Sci. USA 94: 11623– 11626.

89. Horiguchi, Y.,, N. Sugimoto,, and M. Matsuda. 1993. Stimulation of DNA synthesis in osteoblast- like MC3T3-E1 cells by Bordetella bronchiseptica dermonecrotic toxin. Infect. Immun. 61: 3611– 3615.

90. Horiguchi, Y.,, T. Nakai,, and K. Kume. 1991. Effects of Bordetella bronchiseptica dermonecrotic toxin on the structure and function of osteoblastic clone MC3T3-E1 cells. Infect. Immun. 59: 1112– 1116.

91. Horiguchi, Y.,, T. Okada,, N. Sugimoto,, Y. Morikawa,, J. Katahira,, and M. Matsuda. 1995. Effects of Bordetella bronchiseptica dermonecrotizing toxin on bone formation in calvaria of neonatal rats. FEMS Immunol. Med. Microbiol. 12: 29– 32.

92. Horiguchi, Y.,, T. Senda,, N. Sugimoto,, J. Katahira,, and M. Matsuda. 1995. Bordetella bronchiseptica dermonecrotizing toxin stimulates assembly of actin stress fibers and focal adhesions by modifying the small GTP-binding protein rho. J. Cell. Sci. 108: 3243– 3251.

93. Horváth, Z.,, L. Papp,, and B. Éliás. 1972. Studies of Ca and P metabolism in atrophic rhinitis of swine. II. Bone Ca and P contents of healthy and pigs affected with atrophic rhinitis. Acta Vet. Hung. 22: 45– 51.

94. Hoskins, I. C.,, and A. J. Lax. 1996. Constitutive expression of Pasteurella multocida toxin. FEMS Microbiol. Lett. 141: 189– 193.

95. Hoskins, I. C.,, L. H. Thomas,, and A. J. Lax. 1997. Nasal infection with Pasteurella multocida causes proliferation of bladder epithelium in gnotobiotic pigs. Vet. Rec. 140: 22.

96. Il’ina, Z. M.,, and I. Zasukhin. 1975. Role of Pasteurella toxins in the pathogenesis of infectious atrophic rhinitis. Sb. Nauchn. Rab. Sib. Zon Nauch. Vet. Inst. Omsk 25: 76– 86.

97. Ishikawa, H.,, and Y. Isayama. 1987. Evidence for sialyl glycoconjugates as receptors for B. bronchiseptica on swine nasal mucosa. Infect. Immun. 55: 1607– 1609.

98. Iwaki, M.,, K. Kamachi,, N. Heveker,, and T. Konda. 1999. Suppression of platelet aggregation by Bordetella pertussis adenylate cyclase toxin. Infect. Immun. 67: 2763– 2768.

99. Jacob-Dubuisson, F.,, C. Buisine,, N. Mielcarek,, E. Clement,, F. D. Menozzi,, and C. Locht. 1996. Amino-terminal maturation of the Bordetella pertussis filamentous haemagglutinin. Mol. Microbiol. 19: 65– 78.

100. Jacques, M.,, N. Parent,, and B. Foiry. 1988. Adherence of Bordetella bronchiseptica and Pasteurella multocida to porcine nasal epithelial cells. Can. J. Vet. Res. 52: 283– 285.

101. Jutras, I.,, and B. Martineau-Doizé. 1996. Stimulation of osteoclast-like cell formation by Pasteurella multocida toxin from hemopoietic progenitor cells in mouse bone marrow cultures. Can. J. Vet. Res. 60: 34– 39.

102. Kabay, M. J.,, A. R. Mercy,, J. M. Lloyd,, and G. M. Robertson. 1992. Vaccine efficacy for reducing turbinate atrophy and improving growth rate in piggeries with endemic atrophic rhinitis. Aust. Vet. J. 69: 101– 103.

103. Kashimoto, T.,, J. Katahira,, W. R. Cornejo,, M. Masuda,, A. Fukuoh,, T. Matsuzawa,, T. Ohnishi,, and Y. Horiguchi. 1999. Identification of functional domains of Bordetella dermonecrotizing toxin. Infect. Immun. 67: 3727– 3732.

104. Kemeny, L. J. 1972. Experimental atrophic rhinitis produced by Bordetella bronchiseptica culture in young pigs. Cornell Vet. 62: 477– 485.

105. Khelef, N.,, A. Zychlinsky,, and N. Guiso. 1993. Bordetella pertussis induces apoptosis in macrophages: role of adenylate cyclasehemolysin. Infect. Immun. 61: 4064– 4071.

106. Khelef, N.,, C.-M. Bachelet,, B. B. Vargaftig,, and N. Guiso. 1994. Characterization of murine lung inflammation after infection with parental Bordetella pertussis and mutants deficient in adhesins or toxins. Infect. Immun. 62: 2893– 2900.

107. Khelef, N.,, H. Sakamoto,, and N. Guiso. 1992. Both adenylate cyclase and hemolytic activities are required by Bordetella pertussis to initiate infection. Microb. Pathog. 12: 227– 235.

108. Kimman, T. G.,, C. W. G. M. Löwik,, L. J. A. van de Wee-Pals,, C. W. Thesingh,, P. Defize,, E. M. Kamp,, and O. L. M. Bijvoet. 1987. Stimulation of bone resorption by inflamed nasal mucosa, dermonecrotic toxin-containing conditioned medium from Pasteurella multocida, and purified dermonecrotic toxin from P. multocida. Infect. Immun. 55: 2110– 2116.

109. Knapp, S.,, and J. J. Mekalanos. 1988. Two trans-acting regulatory genes (vir and mod) control antigenic modulation in Bordetella pertussis. J. Bacteriol. 170: 5059– 5066.

110. Kobisch, M.,, and P. Novotny. 1990. Identification of a 68-kilodalton outer membrane protein as the major protective antigen of Bordetella bronchiseptica by using specific-pathogen-free piglets. Infect. Immun. 58: 352– 357.

111. Lacerda, H. M.,, A. J. Lax,, and E. Rozengurt. 1996. Pasteurella multocida toxin, a potent intracellularly acting mitogen, induces p125FAK and paxillin tyrosine phosphorylation, actin stress fiber formation, and focal contact assembly in Swiss 3T3 cells. J. Biol. Chem. 271: 439– 445.

112. Lacerda, H. M.,, G. D. Pullinger,, A. J. Lax,, and E. Rozengurt. 1997. Cytotoxic necrotizing factor 1 from Escherichia coli and dermonecrotic toxin from Bordetella bronchiseptica induce p21rho-dependent tyrosine phosphorylation of focal adhesion kinase and paxillin in Swiss 3T3 cells. J. Biol. Chem. 272: 9587– 9596.

113. Lacey, B. W. 1960. Antigenic modulation of Bordetella pertussis. J. Hyg. Camb. 58: 57– 93.

114. Lax, A. J. 1985. Is phase variation in Bordetella caused by mutation and selection? J. Gen. Microbiol. 131: 913– 917.

115. Lax, A. J.,, and A. E. Grigoriadis. 2001. Pasteurella multocida toxin: the mitogenic toxin that stimulates signalling cascades to regulate growth and differentiation. Int. J. Med. Microbiol. 291: 261– 268.

116. Lax, A. J.,, and N. Chanter. 1990. Cloning of the toxin gene from Pasteurella multocida and its role in atrophic rhinitis. J. Gen. Microbiol. 136: 81– 87.

117. Lax, A. J.,, N. Chanter,, G. D. Pullinger,, T. Higgins,, J. M. Staddon,, and E. Rozengurt. 1990. Sequence analysis of the potent mitogenic toxin of Pasteurella multocida. FEBS Lett. 277: 59– 64.

118. Lee, S. W.,, A. Way,, and E. G. Osen. 1986. Purification and subunit heterogeneity of pili of Bordetella bronchiseptica. Infect. Immun. 51: 586– 593.

119. Leininger, E.,, C. A. Ewanowich,, A. Bhargava,, M. S. Peppler,, J. G. Kenimer,, and M. J. Brennan. 1992. Comparative roles of the Arg-Gly-Asp sequence present in the Bordetella pertussis adhesins pertactin and filamentous hemagglutinin. Infect. Immun. 60: 2380– 2385.

120. Leininger, E.,, M. Roberts,, J. G. Kenimer,, I. G. Charles,, N. Fairweather,, P. Novotny,, and M. J. Brennan. 1991. Pertactin, an arggly- asp containing Bordetella pertussis surface protein that promotes adherence of mammalian cells. Proc. Natl. Acad. Sci. USA 88: 345– 349.

121. Leininger, E.,, P. G. Probst,, M. J. Brennan,, and J. G. Kenimer. 1993. Inhibition of Bordetella pertussis filamentous hemagglutinin-mediated cell adherence with monoclonal antibodies. FEMS Microbiol. Lett. 80: 31– 38.

122. Lemichez, E.,, G. Flatau,, M. Bruzzone,, P. Boquet,, and M. Gauthier. 1997. Molecular localization of the Escherichia coli cytotoxic necrotizing factor CNF1 cell-binding and catalytic domains. Mol. Microbiol. 24: 1061– 1070.

123. Lendvai, N.,, T. Magyar,, and G. Semjén. 1992. Cross-protection studies on Bordetella bronchiseptica in mice using an intracerebral challenge model. Vet. Microbiol. 31: 191– 196.

124. Leppla, S. H. 1982. Anthrax toxin edema factor: a bacterial adenylate cyclase that increases cyclic AMP concentrations in eukaryotic cells. Proc. Natl. Acad. Sci. USA 79: 3162– 3166.

125. Lerm, M.,, J. Selzer,, A. Hoffmeyer,, U. R. Rapp,, K. Aktories,, and G. Schmidt. 1999. Deamidation of Cdc42 and Rac by Escherichia coli cytotoxic necrotizing factor 1: activation of c-jun N-terminal kinase in HeLa cells. Infect. Immun. 67: 496– 503.

126. Leslie, P. H.,, and A. D. Gardner. 1931. The phases of Haemophilus pertussis. J. Hyg. Camb. 31: 531– 545.

127. Livey, I.,, and A. C. Wardlaw. 1984. Production and properties of Bordetella pertussis heat labile toxin. J. Med. Microbiol. 17: 91– 103.

128. Locht, C.,, P. Bertin,, F. D. Menozzi,, and G. Renauld. 1993. The filamentous haemagglutinin, a multifaceted adhesion produced by virulent Bordetella spp. Mol. Microbiol. 4: 653– 660.

129. Logomarsino, J. V.,, W. G. Pond,, B. E. Sheffy,, and L. Krook. 1974. Turbinate morphology in pigs inoculated with Bordetella bronchiseptica and fed high or low calcium diets. Cornell Vet. 64: 573– 583.

130. Luker, K. E.,, A. N. Tyler,, G. R. Marshall,, and W. E. Goldman. 1995. Tracheal cytotoxin structural requirements for respiratory epithelial damage in pertussis. Mol. Microbiol. 16: 733– 743.

131. Magyar, T. 1990. Virulence and lienotoxicity of Bordetella bronchiseptica in mice. Vet. Microbiol. 25: 199– 207.

132. Magyar, T.,, N. Chanter,, A. J. Lax,, J. M. Rutter,, and G. A. Hall. 1988. The pathogenesis of turbinate atrophy in pigs caused by Bordetella bronchiseptica. Vet. Microbiol. 18: 135– 146.

133. Magyar, T.,, N. Lendvai,, G. Semjén,, and L. Réthy. 1983. Investigation of the biological activities of Bordetella bronchiseptica. II. Adherence to the target cell. Ann. Immunol. Hung. 23: 361– 366.

134. Magyar, T.,, R. Glávits,, G. D. Pullinger,, and A. J. Lax. 2000. The pathological effect of the bordetella dermonecrotic toxin in mice. Acta Vet. Hung. 48: 397– 406.

135. Mao, J.,, H. Yuan,, W. Xie,, and D. Wu. 1998. Guanine nucleotide exchange factor GEF115 specifically mediates activation of Rho and serum response factor by the G protein α subunit Gα13. Proc. Natl. Acad. Sci. USA 95: 12973– 12976.

136. Martineau-Doizé, B.,, I. Caya,, S. Gagné,, I. Jutras,, and G. Dumas. 1993. Effects of Pasteurella multocida toxin on the osteoclast population of the rat. Comp. Pathol. 108: 81– 91.

137. Masuda, M.,, L. Betancourt,, T. Matsuzawa,, T. Kashimoto,, T. Takao,, Y. Shimonishi,, and Y. Horiguchi. 2000. Activation of Rho through a cross-link with polyamines catalyzed by Bordetella dermonecrotizing toxin. EMBO J. 19: 521– 530.

138. Mattoo, S.,, J. F. Miller,, and P. A. Cotter. 2000. Role of Bordetella bronchiseptica fimbriae in tracheal colonization and development of a humoral immune response. Infect. Immun. 68: 2024– 2033.

139. May, B. J.,, Q. Zhang,, L. L. Li,, M. L. Paustian,, T. S. Whittam,, and V. Kapur. 2001. Complete genomic sequence of Pasteurella multocida, Pm70. Proc. Natl. Acad. Sci. USA 98: 3460– 3465.

140. McMillan, D. J.,, M. Shojaei,, G. S. Chhatwal,, C. A. Guzmán,, and M. J. Walker. 1996. Molecular analysis of the bvg-repressed urease of Bordetella bronchiseptica. Microb. Pathog. 21: 379– 394.

141. Menozzi, F. D.,, R. Mutombo,, G. Renauld,, C. Gantiez,, J. H. Hannah,, E. Leininger,, M. J. Brennan,, and C. Locht. 1994. Heparin-inhabitable lectin activity of the filamentous hemagglutinin adhesin of Bordetella pertussis. Infect. Immun. 62: 769– 778.

142. Miniats, O. P.,, and J. A. Johnson. 1980. Experimental atrophic rhinitis in gnotobiotic pigs. Can. J. Comp. Med. 44: 358– 365.

143. Monack, D. M.,, B. Aricò,, R. Rappuoli,, and S. Falkow. 1989. Phase variants of Bordetella bronchiseptica arise by spontaneous deletions in the vir locus. Mol. Microbiol. 3: 1719– 1728.

144. Montaraz, J. A.,, P. Novotny,, and J. Ivanyi. 1985. Identification of a 68-kilodalton protective protein antigen from Bordetella bronchiseptica. Infect. Immun. 47: 744– 751.

145. Montecucco, C.,, E. Papini,, and G. Schiavo. 1994. Bacterial protein toxins penetrate cells via a four-step mechanism. FEBS Lett. 346: 92– 98.

146. Montminy, M. 1997. Transcriptional regulation by cyclic AMP. Annu. Rev. Biochem. 66: 807– 822.

147. Muirhead, M. R. 1979. Respiratory diseases of pigs. Br. Vet. J. 135: 497– 508.

148. Mullan, P. B.,, and A. J. Lax. 1996. Pasteurella multocida toxin is a mitogen for bone cells in primary culture. Infect. Immun. 64: 959– 965.

149. Mullan, P. B.,, and A. J. Lax. 1998. Pasteurella multocida toxin stimulates bone resorption by osteoclasts via interaction with osteoblasts. Calcif. Tissue Int. 63: 340– 345.

150. Muller, M.,, and A. Hildebrandt. 1993. Nucleotide sequence of the 285 RNA genes from Bordetella pertussis, B. parapertussis, B. bronchiseptica and B. avium, and their implications for phylogenic analysis. Nucleic Acids Res. 21: 3320.

151. Murphy, A. C.,, and E. Rozengurt. 1992. Pasteurella multocida toxin selectively facilitates phosphatidylinositol 4,5-bisphosphate hydrolysis by bombesin, vasopressin, and endothelin. J. Biol. Chem. 267: 25296– 25303.

152. Musser, J. M.,, D. A. Bemis,, H. Ishikawa,, and R. K. Selander. 1987. Clonal diversity and host distribution in Bordetella bronchiseptica. J. Bacteriol. 169: 2793– 2803.

153. Nakai, T.,, A. Sawata,, and K. Kume. 1985. Intracellular locations of dermonectotic toxins in Pasteurella multocida and Bordetella bronchiseptica. Am. J. Vet. Res. 46: 870– 874.

154. Nakai, T.,, K. Kume,, H. Yoshikawa,, T. Oyamada,, and T. Yoshikawa. 1988. Adherence of Pasteurella multocida or Bordetella bronchiseptica to the swine nasal epithelial cell in vitro. Infect. Immun. 56: 234– 240.

155. Nakase, Y. 1957. Studies on Hemophilus bronchisepticus II: phase variation of H. bronchisepticus. Kitasato Arch. Exp. Med. 30: 73– 78.

156. Nakase, Y. 1957. Studies on Hemophilus bronchisepticus III: differences of biological properties between phase I and phase III of H. bronchisepticus. Kitasato Arch. Exp. Med. 30: 79– 84.

157. Njamkepo, E.,, F. Pinot,, D. François,, N. Guiso,, B. S. Polla,, and M. Bachelet. 2000. Adaptive responses of human monocytes infected by Bordetella pertussis: the role of adenylate cyclase hemolysin. J. Cell. Physiol. 183: 91– 99.

158. Ofek, I.,, and E. H. Beachey,. 1980. Bacterial adherence, p. 3– 29. In E. H. Beachey (ed.), Receptors and Recognition, series B6. Chapman and Hall, London, United Kingdom.

159. Parton, R.,, E. Hall,, and A. C. Wardlaw. 1994. Responses to Bordetella pertussis mutant strains and to vaccination in the coughing rat model of pertussis. J. Med. Microbiol. 40: 307– 312.

160. Pedersen, K. B.,, and F. Elling. 1984. The pathogenesis of atrophic rhinitis in pigs induced by toxigenic Pasteurella multocida. J. Comp. Pathol. 94: 203– 214.

161. Pedersen, K. B.,, and K. Barfod. 1981. The aetiological significance of Bordetella bronchiseptica and Pasteurella multocida in atrophic rhinitis of swine. Nord. Vetmed. 33: 513– 522.

162. Pedersen, K. B.,, and K. Barfod. 1982. Effect on the incidence of atrophic rhinitis of vaccination of sows with vaccine Pasteurella multocida toxin. Nord. Vetmed. 34: 293– 302.

163. Penny, R. H. C.,, and J. C. Penny. 1976. Priorities for pig research. Vet. Rec. 99: 451– 453.

164. Petersen, S. K. 1990. The complete nucleotide sequence of the Pasteurella multocida toxin gene and evidence for a transcriptional repressor, TxaR. Mol. Microbiol. 4: 821– 830.

165. Pettit, R. K.,, M. R. Ackermann,, and R. B. Rimler. 1993. Receptor-mediated binding of Pasteurella multocida dermonecrotic toxin to canine osteosarcoma and monkey kidney (vero) cells. Lab. Investig. 69: 94– 100.

166. Pijpers, A.,, B. van Klingeren,, E. J. Schoevers,, J. H. M. Verheijden,, and A. S. J. P. A. M. Van Miert. 1989. In vitro activity of five tetracyclines and some other antimicrobial agents against four porcine respiratory tract pathogens. J. Vet. Pharmacol. Ther. 12: 267– 276.

167. Porter, J. F.,, and A. C. Wardlaw. 1993. Long-term survival of Bordetella bronchiseptica in lakewater and in buffered saline without added nutrients. FEMS Microbiol. Lett. 110: 33– 36.

168. Porter, J. F.,, R. Parton,, and A. C. Wardlaw. 1991. Growth and survival of Bordetella bronchiseptica in natural waters and in buffered saline without added nutrients. Appl. Environ. Microbiol. 57: 1202– 1206.

169. Pullinger, G. D.,, R. Sowdhamini,, and A. J. Lax. 2001. Localization of functional domains of the mitogenic toxin of Pasteurella multocida. Infect. Immun. 69: 7839– 7850.

170. Pullinger, G. D.,, T. E. Adams,, P. B. Mullan,, T. I. Garrod,, and A. J. Lax. 1996. Cloning, expression, and molecular characterization of the dermonecrotic toxin gene of Bordetella spp. Infect. Immun. 64: 4163– 4171.

171. Register, K. B. 2001. Novel genetic and phenotypic heterogeneity in Bordetella bronchiseptica pertactin. Infect. Immun. 69: 1917– 1921.

172. Register, K. B.,, and M. R. Ackermann. 1997. A highly adherent phenotype associated with virulent Bvg +-phase swine isolates of Bordetella bronchiseptica grown under modulating conditions. Infect. Immun. 65: 5295– 5300.

173. Renauld-Mongenie, G.,, J. Cornette,, N. Mielcarek,, F. D. Menozzi,, and C. Locht. 1996. Distinct roles of the N-terminal and C-terminal precursor domains in the biogenesis of the Bordetella pertussis filamentous hemagglutinin. J. Bacteriol. 178: 1053– 1060.

174. Ridley, A. J. 1996. Rho: theme and variations. Curr. Biol. 6: 1256– 1264.

175. Ross, R. F.,, J. R. Duncan,, and W. P. Switzer. 1963. Turbinate atrophy in swine produced by pure cultures of Bordetella bronchiseptica. Vet. Med. 58: 566– 570.

176. Ross, R. F.,, W. P. Switzer,, and J. P. Duncan. 1967. Comparison of pathogenicity of various isolates of Bordetella bronchiseptica in young pigs. Can. J. Comp. Med. 31: 53– 57.

177. Roy, C. R.,, J. F. Miller,, and S. Falkow. 1989. The bvgA gene of Bordetella pertussis encodes a transcriptional activator required for coordinate regulation of several virulence genes. J. Bacteriol. 171: 6338– 6344.

178. Rozengurt, E.,, T. Higgins,, N. Chanter,, A. J. Lax,, and J. M. Staddon. 1990. Pasteurella multocida toxin: potent mitogen for cultured fibroblasts. Proc. Natl. Acad. Sci. USA 87: 123– 127.

179. Rutter, J. M. 1981. Quantitative observations on Bordetella bronchiseptica infection in atrophic rhinitis of pigs. Vet. Rec. 108: 451– 454.

180. Rutter, J. M. 1983. Virulence of Pasteurella multocida in atrophic rhinitis of gnotobiotic pigs infected with Bordetella bronchiseptica. Res. Vet. Sci. 34: 287.

181. Rutter, J. M. 1985. Atrophic rhinitis in swine. Adv. Vet. Sci. Comp. Med. 29: 239– 279.

182. Rutter, J. M.,, and A. Mackenzie. 1984. Pathogenesis of atrophic rhinitis in pigs: a new perspective. Vet. Rec. 114: 89– 90.

183. Rutter, J. M.,, and X. Rojas. 1982. Atrophic rhinitis in gnotobiotic piglets: differences in the pathogenicity of Pasteurella multocida in combined infections with Bordetella bronchiseptica. Vet. Rec. 110: 531– 535.

184. Rutter, J. M.,, L. M. Francis,, and B. F. Sansom. 1982. Virulence of Bordetella bronchiseptica from pigs with or without atrophic rhinitis. J. Med. Microbiol. 15: 105– 116.

185. Sakurai, Y.,, H. Suzuki,, and E. Terada. 1993. Purification and characterisation of haemagglutinin from Bordetella bronchiseptica. J. Med. Microbiol. 39: 388– 392.

186. Savelkoul, P. H.,, B. Kremer,, J. G. Kusters,, B. A. van der Zeijst,, and W. Gaastra. 1993. Invasion of HeLa cells by Bordetella bronchiseptica. Microb. Pathog. 14: 161– 168.

187. Savelkoul, P. H. M.,, D. P. G. deKerf,, R. J. Willems,, F. R. Mooi,, B. A. M. van der Zeijst,, and W. Gaastra. 1996. Characterization of the fim2 and fim3 fimbrial subunit genes of Bordetella bronchiseptica: roles of Fim2 and Fim3 fimbriae and flagella in adhesion. Infect. Immun. 64: 5098– 5105.

188. Scarlato, V.,, B. Arico,, A. Prugnola,, and R. Rappuoli. 1991. Sequential activation and environmental regulation of virulence genes in Bordetella pertussis. EMBO J. 10: 3971– 3975.

189. Scarlato, V.,, B. Arico,, M. Domenighini,, and R. Rappuoli. 1993. Environmental regulation of virulence factors in Bordetella species. Bioessays 15: 99– 104.

190. Schipper, H.,, G. F. Krohne,, and R. Gross. 1994. Epithelial cell invasion and survival of Bordetella bronchiseptica. Infect. Immun. 62: 3008– 3011.

191. Schmidt, G.,, U.-M. Goehring,, J. Schirmer,, M. Lerm,, and K. Aktories. 1999. Identification of the C-terminal part of Bordetella dermonecrotic toxin as a transglutaminase for Rho GTPases. J. Biol. Chem. 274: 31875– 31881.

192. Schneider, D. R.,, and C. D. Parker. 1983. Effect of pyridines on phenotypic properties of Bordetella pertussis. Infect. Immun. 38: 548– 553.

193. Seifert, H. 1971. Genetic aspects of atrophic rhinitis in the pig. Monatsh. Vetmed. 26: 770– 772.

194. Semjén, G.,, and T. Magyar. 1985. A bovine haemagglutinin of Bordetella bronchiseptica responsible for adherence. Acta Vet. Hung. 33: 129– 136.

195. Seo, B.,, E. W. Choy,, S. Maudsley,, W. E. Miller,, B. A. Wilson,, and L. M. Luttrell. 2000. Pasteurella multocida toxin stimulates mitogen- activated protein kinase via Gq/11-dependent transactivation of the epidermal growth factor receptor. J. Biol. Chem. 275: 2239– 2245.

196. Shimizu, T.,, M. Nakagawa,, S. Shibata,, and K. Suzuki. 1971. Atrophic rhinitis produced by intranasal inoculation of Bordetella bronchiseptica in hysterectomy produced colostrum-deprived pigs. Cornell Vet. 61: 696– 705.

197. Sisak, F.,, M. Gois,, and F. Kuksa. 1978. The sensitivity of the strains of Bordetella bronchiseptica, Pasteurella multocida and Mycoplasma hyorhinis, isolated from pigs, to antibiotics and chemotherapeutics. Vet. Med. ( Prague) 23: 531.

198. Smith, A. M.,, C. A. Guzman,, and M. J. Walker. 2001. The virulence factors of Bordetella pertussis: a matter of control. FEMS Microbiol. Rev. 25: 309– 333.

199. Smith, I. M.,, C. J. Giles,, and A. J. Baskerville. 1982. The immunisation of pigs against experimental infection with Bordetella bronchiseptica. Vet. Rec. 110: 488– 494.

200. Smyth, M. G.,, I. G. Sumner,, and A. J. Lax. 1999. Reduced pH causes structural changes in the potent mitogenic toxin of Pasteurella multocida. FEMS Microbiol. Lett. 180: 15– 20.

201. Smyth, M. G.,, R. W. Pickersgill,, and A. J. Lax. 1995. The potent mitogen Pasteurella multocida toxin is highly resistant to proteolysis but becomes susceptible at lysosomal pH. FEBS Lett. 360: 62– 66.

202. Somlyo, A. P.,, and A. V. Somlyo. 2000. Signal transduction by G-proteins, Rho-kinase and protein phosphatase to smooth muscle and non-muscle myosin II. J. Physiol. 522: 177– 185.

203. Staddon, J. M.,, N. Chanter,, A. J. Lax,, T. E. Higgins,, and E. Rozengurt. 1990. Pasteurella multocida toxin, a potent mitogen, stimulates protein kinase C-dependent and -independent protein phosphorylation in Swiss 3T3 cells. J. Biol. Chem. 265: 11841– 11848.

204. Staddon, J. M.,, C. J. Barker,, A. C. Murphy,, N. Chanter,, A. J. Lax,, R. H. Michell,, and E. Rozengurt. 1991. Pasteurella multocida toxin, a potent mitogen, increases inositol 1,4,5- trisphosphate and mobilizes Ca2+ in Swiss 3T3 cells. J. Biol. Chem. 266: 4840– 4847.

205. Sterner-Kock, A.,, B. Lanske,, S. Überschär,, and M. J. Atkinson. 1995. Effects of the Pasteurella multocida toxin on osteoblastic cells in vitro. Vet. Pathol. 32: 274– 279.

206. Stibitz, S.,, W. Aaronson,, D. Monack,, and S. Falkow. 1989. Phase variation in Bordetella pertussis by frameshift mutation in a gene for a novel two-component system. Nature 338: 266– 269.

207. Straw, B. E.,, A. D. Leman,, and R. A. Robinson. 1984. Pneumonia and atrophic rhinitis in pigs from a test station: a follow-up study. J. Am. Vet. Med. Assoc. 185: 1544– 1546.

208. Straw, B. E.,, E. J. Burgi,, and H. D. Hilley. 1983. Pneumonia and atrophic rhinitis in pigs from a test station. J. Am. Vet. Med. Assoc. 182: 607– 611.

209. Suda, T.,, N. Takahashi,, N. Udagawa,, E. Jimi,, M. T. Gillespie,, and T. J. Martin. 1999. Modulation of osteoclast differentiation and function by the new members of the tumor necrosis factor receptor and ligand families. Endocr. Rev. 20: 345– 357.

210. Switzer, W. P. 1956. Infectious atrophic rhinitis: concept that several agents may cause turbinate atrophy. Am. J. Vet. Res. 17: 478– 484.

211. Switzer, W. P. 1963. Elimination of Bordetella bronchiseptica from the nasal cavity of swine by sulphonamide therapy. Vet. Med. 58: 571– 574.

212. Switzer, W. P., 1981. Bordetellosis, p. 497– 507. In A. D. Leman,, R. D. Glock,, W. L. Mengeling,, R. H. C. Penny,, E. Scholl,, and B. Straw (ed.), Diseases of Swine, 5th ed. Iowa State University Press, Ames..

213. Switzer, W. P.,, and D. O. Farrington,. 1975. Infectious atrophic rhinitis, p. 687– 711. In H. W. Dunne, and A. D. Leman (ed.), Diseases of Swine, 4th ed. Iowa State University Press, Ames..

214. Taylor, S. S.,, J. A. Buechler,, and W. Yonemoto. 1990. cAMP-dependent protein kinase: framework for a diverse family of regulatory enzymes. Annu. Rev. Biochem. 59: 971– 1005.

215. Thomas, W.,, G. D. Pullinger,, A. J. Lax,, and E. Rozengurt. 2001. Escherichia coli cytotoxic necrotizing factor and Pasteurella multocida toxin induce FAK autophosphorylation and src association. Infect. Immun. 69: 5931– 5935.

216. Thomas, W.,, Z. K. Ascott,, D. Harmey,, L. W. Slice,, E. Rozengurt,, and A. J. Lax. 2001. Cytotoxic necrotizing factor from Escherichia coli induces RhoA-dependent expression of the cyclooxygenase-2 gene. Infect. Immun. 69: 6839– 6845.

217. Tornoe, N.,, and N. C. Nielsen. 1976. Inoculation experiments with Bordetella bronchiseptica strains in SPF pigs. Nord. Vetmed. 28: 233– 242.

218. Tornoe, N.,, N. C. Nielsen,, and J. Svendsen. 1976. Bordetella bronchiseptica isolations from the nasal cavity of pigs in relation to atrophic rhinitis. Nord. Vetmed. 28: 1.

219. Tuomanen, E. 1986. Piracy of adhesins: attachment of superinfecting pathogens to respiratory cilia by secreted adhesins of Bordetella pertussis. Infect. Immun. 54: 905– 908.

220. vanDiemen, P. M.,, M. F. deJong,, G. de Vries Reilingh,, and J. W. van der Hel P, Schrama. 1994. Intranasal administration of Pasteurella multocida toxin in a challenge-exposure model used to induce subclinical signs of atrophic rhinitis in pigs. Am. J. Vet. Res. 55: 49– 54.

221. van Diemen, P. M.,, G. de Vries Reilingh,, and H. K. Parmentier. 1996. Effect of Pasteurella multocida toxin on in vivo immune responses in piglets. Vet. Q. 18: 141– 146.

222. Walker, K. E.,, and A. A. Weiss. 1994. Characterization of the dermonecrotic toxin in members of the genus Bordetella. Infect. Immun. 62: 3817– 3828.

223. Wang, D.,, J. R. Grammer,, C. S. Cobbs,, J. E. Stewart,, Z. Liu,, R. Rhoden,, T. P. Hecker,, Q. Ding,, and C. L. Gladson. 2000. p125 focal adhesion kinase promotes malignant astrocytoma cell proliferation in vivo. J. Cell Sci. 113: 4221– 4230.

224. Ward, P. N.,, A. J. Miles,, I. G. Sumner,, L. H. Thomas,, and A. J. Lax. 1998. Activity of the mitogenic Pasteurella multocida toxin requires an essential C-terminal residue. Infect. Immun. 66: 5636– 5642.

225. Weingart, C. L.,, and A. A. Weiss. 2000. Bordetella pertussis virulence factors affect phagocytosis by human neutrophils. Infect. Immun. 68: 1735– 1739.

226. Weiss, A. A.,, and M. S. M. Goodwin. 1989. Bordetella pertussis mutants in the infant mouse model. Infect. Immun. 57: 3757– 3764.

227. Weiss, A. A.,, and S. Falkow. 1984. Genetic analysis of phase change in Bordetella pertussis. Infect. Immun. 43: 263– 269.

228. Weiss, A. A.,, E. L. Hewlett,, G. A. Myers,, and S. Falkow. 1984. Pertussis toxin and extracytoplasmic adenylate cyclase as virulence factors of Bordetella pertussis. J. Infect. Dis. 150: 219– 221.

229. Wilson, B. A.,, X. Zhu,, M. Ho,, and L. Lu. 1997. Pasteurella multocida toxin activates the inositol triphosphate signaling pathway in Xenopus oocytes via G qα-coupled phospholipase C-β1. J. Biol. Chem. 272: 1268– 1275.

230. Winstanley, C.,, and C. A. Hart. 2001. Type III secretion systems and pathogenicity islands. J. Med. Microbiol. 50: 116– 126.

231. Winstanley, C.,, B. A. Hales,, L. M. Sibanda,, S. Dawson,, R. M. Gaskell,, and C. A. Hart. 2000. Detection of type III secretion system genes in animal isolates of Bordetella bronchiseptica. Vet. Microbiol. 72: 329– 337.

232. Wolff, J.,, and G. H. Cook. 1973. Activity of thyroid membrane adenylate cyclase. J. Biol. Chem. 248: 350– 355.

233. Wolff, J.,, G. H. Cook,, A. R. Goldhammer,, and S. A. Berkowitz. 1980. Calmodulin activates prokaryotic adenylate cyclase. Proc. Natl. Acad. Sci. USA 77: 3841– 3844.

234. Woolfrey, B. F.,, and J. A. Moody. 1991. Human infections associated with Bordetella bronchiseptica. Clin. Microbiol. Rev. 4: 243– 255.

235. Yokomizo, Y.,, and T. Shimizu. 1979. Adherence of Bordetella bronchiseptica to swine nasal epithelial cells and its possible role in virulence. Res. Vet. Sci. 27: 15– 21.

236. Yuk, M. H.,, E. T. Harvill,, and J. F. Miller. 1998. The BvgAS virulence control system regulates type III secretion in Bordetella bronchiseptica. Mol. Microbiol. 28: 945– 959.

237. Yuk, M. H.,, E. T. Harvill,, P. A. Cotter,, and J. F. Miller. 2000. Modulation of host immune responses, induction of apoptosis and inhibition of NF-kappaB activation by the Bordetella type III secretion system. Mol. Microbiol. 35: 991– 1004.

238. Zhang, Y. L.,, and R. D. Sekura. 1991. Purification and characterization of the heat-labile toxin of Bordetella pertussis. Infect. Immun. 59: 3754– 3759.

239. Zywietz, A.,, A. Gohla,, M. Shmelz,, G. Schultz,, and S. Offermanns. 2001. Pleiotropic effects of Pasteurella multocida toxin are mediated by Gq-dependent and -independent mechanisms. J. Biol. Chem. 276: 3840– 3845.