This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Harvill, E. T.
Right arrow Articles by Miller, J. F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Harvill, E. T.
Right arrow Articles by Miller, J. F.

 Previous Article  |  Next Article 

Infection and Immunity, March 1999, p. 1493-1500, Vol. 67, No. 3
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Probing the Function of Bordetella bronchiseptica Adenylate Cyclase Toxin by Manipulating Host Immunity

Eric T. Harvill, Peggy A. Cotter, Ming Huam Yuk, and Jeff F. Miller*

Department of Microbiology and Immunology, UCLA School of Medicine, Los Angeles, California 90095-1747

Received 23 October 1998/Returned for modification 19 November 1998/Accepted 9 December 1998

We have examined the role of adenylate cyclase-hemolysin (CyaA) by constructing an in-frame deletion in the Bordetella bronchiseptica cyaA structural gene and comparing wild-type and cyaA deletion strains in natural host infection models. Both the wild-type strain RB50 and its adenylate cyclase toxin deletion (Delta cyaA) derivative efficiently establish persistent infections in rabbits, rats, and mice following low-dose inoculation. In contrast, an inoculation protocol that seeds the lower respiratory tract revealed significant differences in bacterial numbers and in polymorphonuclear neutrophil recruitment in the lungs from days 5 to 12 postinoculation. We next explored the effects of disarming specific aspects of the immune system on the relative phenotypes of wild-type and Delta cyaA bacteria. SCID, SCID-beige, or RAG-1-/- mice succumbed to lethal systemic infection following high- or low-dose intranasal inoculation with the wild-type strain but not the Delta cyaA mutant. Mice rendered neutropenic by treatment with cyclophosphamide or by knockout mutation in the granulocyte colony-stimulating factor locus were highly susceptible to lethal infection by either wild-type or Delta cyaA strains. These results reveal the significant role played by neutrophils early in B. bronchiseptica infection and by acquired immunity at later time points and suggest that phagocytic cells are a primary in vivo target of the Bordetella adenylate cyclase toxin.


* Corresponding author. Mailing address: Department of Microbiology and Immunology, UCLA School of Medicine, Center for the Health Sciences, 10833 LeConte Ave., Los Angeles, CA 90095-1747. Phone: (310) 206-7926. Fax: (310) 206-3865. E-mail: jfmiller{at}ucla.edu.


Infection and Immunity, March 1999, p. 1493-1500, Vol. 67, No. 3
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.



This article has been cited by other articles:

  • Buboltz, A. M., Nicholson, T. L., Weyrich, L. S., Harvill, E. T. (2009). Role of the Type III Secretion System in a Hypervirulent Lineage of Bordetella bronchiseptica. Infect. Immun. 77: 3969-3977 [Abstract] [Full Text]  
  • Nicholson, T. L., Brockmeier, S. L., Loving, C. L. (2009). Contribution of Bordetella bronchiseptica Filamentous Hemagglutinin and Pertactin to Respiratory Disease in Swine. Infect. Immun. 77: 2136-2146 [Abstract] [Full Text]  
  • Andreasen, C., Carbonetti, N. H. (2009). Role of Neutrophils in Response to Bordetella pertussis Infection in Mice. Infect. Immun. 77: 1182-1188 [Abstract] [Full Text]  
  • Buboltz, A. M., Nicholson, T. L., Parette, M. R., Hester, S. E., Parkhill, J., Harvill, E. T. (2008). Replacement of Adenylate Cyclase Toxin in a Lineage of Bordetella bronchiseptica. J. Bacteriol. 190: 5502-5511 [Abstract] [Full Text]  
  • Williams, C. L., Haines, R., Cotter, P. A. (2008). Serendipitous Discovery of an Immunoglobulin-Binding Autotransporter in Bordetella Species. Infect. Immun. 76: 2966-2977 [Abstract] [Full Text]  
  • Goebel, E. M., Wolfe, D. N., Elder, K., Stibitz, S., Harvill, E. T. (2008). O Antigen Protects Bordetella parapertussis from Complement. Infect. Immun. 76: 1774-1780 [Abstract] [Full Text]  
  • Mann, P., Goebel, E., Barbarich, J., Pilione, M., Kennett, M., Harvill, E. (2007). Use of a Genetically Defined Double Mutant Strain of Bordetella bronchiseptica Lacking Adenylate Cyclase and Type III Secretion as a Live Vaccine. Infect. Immun. 75: 3665-3672 [Abstract] [Full Text]  
  • Basler, M., Knapp, O., Masin, J., Fiser, R., Maier, E., Benz, R., Sebo, P., Osicka, R. (2007). Segments Crucial for Membrane Translocation and Pore-forming Activity of Bordetella Adenylate Cyclase Toxin. J. Biol. Chem. 282: 12419-12429 [Abstract] [Full Text]  
  • Fiser, R., Masin, J., Basler, M., Krusek, J., Spulakova, V., Konopasek, I., Sebo, P. (2007). Third Activity of Bordetella Adenylate Cyclase (AC) Toxin-Hemolysin: MEMBRANE TRANSLOCATION OF AC DOMAIN POLYPEPTIDE PROMOTES CALCIUM INFLUX INTO CD11b+ MONOCYTES INDEPENDENTLY OF THE CATALYTIC AND HEMOLYTIC ACTIVITIES. J. Biol. Chem. 282: 2808-2820 [Abstract] [Full Text]  
  • Siciliano, N. A., Skinner, J. A., Yuk, M. H. (2006). Bordetella bronchiseptica Modulates Macrophage Phenotype Leading to the Inhibition of CD4+ T Cell Proliferation and the Initiation of a Th17 Immune Response. J. Immunol. 177: 7131-7138 [Abstract] [Full Text]  
  • Irie, Y., Preston, A., Yuk, M. H. (2006). Expression of the Primary Carbohydrate Component of the Bordetella bronchiseptica Biofilm Matrix Is Dependent on Growth Phase but Independent of Bvg Regulation.. J. Bacteriol. 188: 6680-6687 [Abstract] [Full Text]  
  • Inatsuka, C. S., Julio, S. M., Cotter, P. A. (2005). Bordetella filamentous hemagglutinin plays a critical role in immunomodulation, suggesting a mechanism for host specificity. Proc. Natl. Acad. Sci. USA 102: 18578-18583 [Abstract] [Full Text]  
  • Zeng, X., Moore, T. A., Newstead, M. W., Deng, J. C., Kunkel, S. L., Luster, A. D., Standiford, T. J. (2005). Interferon-Inducible Protein 10, but Not Monokine Induced by Gamma Interferon, Promotes Protective Type 1 Immunity in Murine Klebsiella pneumoniae Pneumonia. Infect. Immun. 73: 8226-8236 [Abstract] [Full Text]  
  • Kostina, E., Ofek, I., Crouch, E., Friedman, R., Sirota, L., Klinger, G., Sahly, H., Keisari, Y. (2005). Noncapsulated Klebsiella pneumoniae Bearing Mannose-Containing O Antigens Is Rapidly Eradicated from Mouse Lung and Triggers Cytokine Production by Macrophages following Opsonization with Surfactant Protein D. Infect. Immun. 73: 8282-8290 [Abstract] [Full Text]  
  • Julio, S. M., Cotter, P. A. (2005). Characterization of the Filamentous Hemagglutinin-Like Protein FhaS in Bordetella bronchiseptica. Infect. Immun. 73: 4960-4971 [Abstract] [Full Text]  
  • Edwards, J. A., Groathouse, N. A., Boitano, S. (2005). Bordetella bronchiseptica Adherence to Cilia Is Mediated by Multiple Adhesin Factors and Blocked by Surfactant Protein A. Infect. Immun. 73: 3618-3626 [Abstract] [Full Text]  
  • Carbonetti, N. H., Artamonova, G. V., Andreasen, C., Bushar, N. (2005). Pertussis Toxin and Adenylate Cyclase Toxin Provide a One-Two Punch for Establishment of Bordetella pertussis Infection of the Respiratory Tract. Infect. Immun. 73: 2698-2703 [Abstract] [Full Text]  
  • Mattoo, S., Cherry, J. D. (2005). Molecular Pathogenesis, Epidemiology, and Clinical Manifestations of Respiratory Infections Due to Bordetella pertussis and Other Bordetella Subspecies. Clin. Microbiol. Rev. 18: 326-382 [Abstract] [Full Text]  
  • Reissinger, A., Skinner, J. A., Yuk, M. H. (2005). Downregulation of Mitogen-Activated Protein Kinases by the Bordetella bronchiseptica Type III Secretion System Leads to Attenuated Nonclassical Macrophage Activation. Infect. Immun. 73: 308-316 [Abstract] [Full Text]  
  • Widney, D. P., Hu, Y., Foreman-Wykert, A. K., Bui, K. C., Nguyen, T. T., Lu, B., Gerard, C., Miller, J. F., Smith, J. B. (2005). CXCR3 and Its Ligands Participate in the Host Response to Bordetella bronchiseptica Infection of the Mouse Respiratory Tract but Are Not Required for Clearance of Bacteria from the Lung. Infect. Immun. 73: 485-493 [Abstract] [Full Text]  
  • Irie, Y., Mattoo, S., Yuk, M. H. (2004). The Bvg Virulence Control System Regulates Biofilm Formation in Bordetella bronchiseptica. J. Bacteriol. 186: 5692-5698 [Abstract] [Full Text]  
  • Skinner, J. A., Reissinger, A., Shen, H., Yuk, M. H. (2004). Bordetella Type III Secretion and Adenylate Cyclase Toxin Synergize to Drive Dendritic Cells into a Semimature State. J. Immunol. 173: 1934-1940 [Abstract] [Full Text]  
  • Vougier, S., Mary, J., Dautin, N., Vinh, J., Friguet, B., Ladant, D. (2004). Essential Role of Methionine Residues in Calmodulin Binding to Bordetella pertussis Adenylate Cyclase, as Probed by Selective Oxidation and Repair by the Peptide Methionine Sulfoxide Reductases. J. Biol. Chem. 279: 30210-30218 [Abstract] [Full Text]  
  • Ross, P. J., Lavelle, E. C., Mills, K. H. G., Boyd, A. P. (2004). Adenylate Cyclase Toxin from Bordetella pertussis Synergizes with Lipopolysaccharide To Promote Innate Interleukin-10 Production and Enhances the Induction of Th2 and Regulatory T Cells. Infect. Immun. 72: 1568-1579 [Abstract] [Full Text]  
  • Liu, M., Gingery, M., Doulatov, S. R., Liu, Y., Hodes, A., Baker, S., Davis, P., Simmonds, M., Churcher, C., Mungall, K., Quail, M. A., Preston, A., Harvill, E. T., Maskell, D. J., Eiserling, F. A., Parkhill, J., Miller, J. F. (2004). Genomic and Genetic Analysis of Bordetella Bacteriophages Encoding Reverse Transcriptase-Mediated Tropism-Switching Cassettes. J. Bacteriol. 186: 1503-1517 [Abstract] [Full Text]  
  • Carbonetti, N. H., Artamonova, G. V., Mays, R. M., Worthington, Z. E. V. (2003). Pertussis Toxin Plays an Early Role in Respiratory Tract Colonization by Bordetella pertussis. Infect. Immun. 71: 6358-6366 [Abstract] [Full Text]  
  • El-Azami-El-Idrissi, M., Bauche, C., Loucka, J., Osicka, R., Sebo, P., Ladant, D., Leclerc, C. (2003). Interaction of Bordetella pertussis Adenylate Cyclase with CD11b/CD18: ROLE OF TOXIN ACYLATION AND IDENTIFICATION OF THE MAIN INTEGRIN INTERACTION DOMAIN. J. Biol. Chem. 278: 38514-38521 [Abstract] [Full Text]  
  • Burns, V. C., Pishko, E. J., Preston, A., Maskell, D. J., Harvill, E. T. (2003). Role of Bordetella O Antigen in Respiratory Tract Infection. Infect. Immun. 71: 86-94 [Abstract] [Full Text]  
  • Heininger, U., Cotter, P. A., Fescemyer, H. W., Martinez de Tejada, G., Yuk, M. H., Miller, J. F., Harvill, E. T. (2002). Comparative Phenotypic Analysis of the Bordetella parapertussis Isolate Chosen for Genomic Sequencing. Infect. Immun. 70: 3777-3784 [Abstract] [Full Text]  
  • Sisti, F., Fernandez, J., Rodriguez, M. E., Lagares, A., Guiso, N., Hozbor, D. F. (2002). In Vitro and In Vivo Characterization of a Bordetella bronchiseptica Mutant Strain with a Deep Rough Lipopolysaccharide Structure. Infect. Immun. 70: 1791-1798 [Abstract] [Full Text]  
  • Guermonprez, P., Khelef, N., Blouin, E., Rieu, P., Ricciardi-Castagnoli, P., Guiso, N., Ladant, D., Leclerc, C. (2001). The Adenylate Cyclase Toxin of Bordetella pertussis Binds to Target Cells via the {alpha}M{beta}2 Integrin (Cd11b/Cd18). JEM 193: 1035-1044 [Abstract] [Full Text]  
  • Register, K. B., Ducey, T. F., Brockmeier, S. L., Dyer, D. W. (2001). Reduced Virulence of a Bordetella bronchiseptica Siderophore Mutant in Neonatal Swine. Infect. Immun. 69: 2137-2143 [Abstract] [Full Text]  
  • Harvill, E. T., Preston, A., Cotter, P. A., Allen, A. G., Maskell, D. J., Miller, J. F. (2000). Multiple Roles for Bordetella Lipopolysaccharide Molecules during Respiratory Tract Infection. Infect. Immun. 68: 6720-6728 [Abstract] [Full Text]  
  • Weingart, C. L., Mobberley-Schuman, P. S., Hewlett, E. L., Gray, M. C., Weiss, A. A. (2000). Neutralizing Antibodies to Adenylate Cyclase Toxin Promote Phagocytosis of Bordetella pertussis by Human Neutrophils. Infect. Immun. 68: 7152-7155 [Abstract] [Full Text]  
  • Forde, C. B., Shi, X., Li, J., Roberts, M. (1999). Bordetella bronchiseptica-Mediated Cytotoxicity to Macrophages Is Dependent on bvg-Regulated Factors, Including Pertactin. Infect. Immun. 67: 5972-5978 [Abstract] [Full Text]  
  • Harvill, E. T., Cotter, P. A., Miller, J. F. (1999). Pregenomic Comparative Analysis between Bordetella bronchiseptica RB50 and Bordetella pertussis Tohama I in Murine Models of Respiratory Tract Infection. Infect. Immun. 67: 6109-6118 [Abstract] [Full Text]