Abstract
Bordetella pertussis expresses factors such as filamentous hemagglutinin, agglutinogens, pertactin, and pertussis toxin, which participate in bacterial adhesion; pertussis toxin, dermonecrotic toxin, lipopolysaccharide, and tracheal cytotoxin, which are responsible for toxic effects; and adenylate cyclase-hemolysin, which is required to initiate infection. By using a murine respiratory model, we showed that the RGD sequences of filamentous hemagglutinin and pertactin are important for bacterial persistence. However, mutants deficient in filamentous hemagglutinin and agglutinogens or in pertactin and the RGD sequence of filamentous hemagglutinin behaved as did wild-type B. pertussis, i.e., induced bronchopneumonia, alveolitis, and an influx of macrophages, lymphocytes, and polymorphonuclear leukocytes into bronchoalveolar lavage fluids. These results suggest that these adhesins are not involved in the induction of pulmonary lesions following infection. The intensity of inflammation was markedly reduced after infection with mutants deficient in either hemolytic activity or pertussis toxin expression, whereas a mutant devoid of adenylate cyclase activity behaved as did the avirulent mutant. Pertussis toxin and adenylate cyclase-hemolysin may act indirectly by altering immune cell functions and thus allowing other factors, such as filamentous hemagglutinin, agglutinogens, and pertactin, to trigger adhesion and lipopolysaccharide, dermonecrotic toxin, and tracheal cytotoxin to induce their toxic effects. However, it is possible that pertussis toxin is also responsible for the induction of some pulmonary alterations.
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- Antoine R., Locht C. Roles of the disulfide bond and the carboxy-terminal region of the S1 subunit in the assembly and biosynthesis of pertussis toxin. Infect Immun. 1990 Jun;58(6):1518–1526. doi: 10.1128/iai.58.6.1518-1526.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Aricò B., Scarlato V., Monack D. M., Falkow S., Rappuoli R. Structural and genetic analysis of the bvg locus in Bordetella species. Mol Microbiol. 1991 Oct;5(10):2481–2491. doi: 10.1111/j.1365-2958.1991.tb02093.x. [DOI] [PubMed] [Google Scholar]
- Charles I. G., Dougan G., Pickard D., Chatfield S., Smith M., Novotny P., Morrissey P., Fairweather N. F. Molecular cloning and characterization of protective outer membrane protein P.69 from Bordetella pertussis. Proc Natl Acad Sci U S A. 1989 May;86(10):3554–3558. doi: 10.1073/pnas.86.10.3554. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chen W., Alley M. R., Manktelow B. W., Hopcroft D., Bennett R. Pneumonia in lambs inoculated with Bordetella parapertussis: bronchoalveolar lavage and ultrastructural studies. Vet Pathol. 1988 Jul;25(4):297–303. doi: 10.1177/030098588802500408. [DOI] [PubMed] [Google Scholar]
- Confer D. L., Eaton J. W. Phagocyte impotence caused by an invasive bacterial adenylate cyclase. Science. 1982 Sep 3;217(4563):948–950. doi: 10.1126/science.6287574. [DOI] [PubMed] [Google Scholar]
- Finn T. M., Shahin R., Mekalanos J. J. Characterization of vir-activated TnphoA gene fusions in Bordetella pertussis. Infect Immun. 1991 Sep;59(9):3273–3279. doi: 10.1128/iai.59.9.3273-3279.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Glaser P., Sakamoto H., Bellalou J., Ullmann A., Danchin A. Secretion of cyclolysin, the calmodulin-sensitive adenylate cyclase-haemolysin bifunctional protein of Bordetella pertussis. EMBO J. 1988 Dec 1;7(12):3997–4004. doi: 10.1002/j.1460-2075.1988.tb03288.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Guiso N., Rocancourt M., Szatanik M., Alonso J. M. Bordetella adenylate cyclase is a virulence associated factor and an immunoprotective antigen. Microb Pathog. 1989 Nov;7(5):373–380. doi: 10.1016/0882-4010(89)90040-5. [DOI] [PubMed] [Google Scholar]
- Katada T., Oinuma M., Ui M. Mechanisms for inhibition of the catalytic activity of adenylate cyclase by the guanine nucleotide-binding proteins serving as the substrate of islet-activating protein, pertussis toxin. J Biol Chem. 1986 Apr 15;261(11):5215–5221. [PubMed] [Google Scholar]
- Khelef N., Sakamoto H., Guiso N. Both adenylate cyclase and hemolytic activities are required by Bordetella pertussis to initiate infection. Microb Pathog. 1992 Mar;12(3):227–235. doi: 10.1016/0882-4010(92)90057-u. [DOI] [PubMed] [Google Scholar]
- Khelef N., Zychlinsky A., Guiso N. Bordetella pertussis induces apoptosis in macrophages: role of adenylate cyclase-hemolysin. Infect Immun. 1993 Oct;61(10):4064–4071. doi: 10.1128/iai.61.10.4064-4071.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Locht C., Geoffroy M. C., Renauld G. Common accessory genes for the Bordetella pertussis filamentous hemagglutinin and fimbriae share sequence similarities with the papC and papD gene families. EMBO J. 1992 Sep;11(9):3175–3183. doi: 10.1002/j.1460-2075.1992.tb05394.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Menozzi F. D., Gantiez C., Locht C. Interaction of the Bordetella pertussis filamentous hemagglutinin with heparin. FEMS Microbiol Lett. 1991 Feb;62(1):59–64. doi: 10.1111/j.1574-6968.1991.tb04417.x. [DOI] [PubMed] [Google Scholar]
- Pittman M., Furman B. L., Wardlaw A. C. Bordetella pertussis respiratory tract infection in the mouse: pathophysiological responses. J Infect Dis. 1980 Jul;142(1):56–66. doi: 10.1093/infdis/142.1.56. [DOI] [PubMed] [Google Scholar]
- Relman D. A., Domenighini M., Tuomanen E., Rappuoli R., Falkow S. Filamentous hemagglutinin of Bordetella pertussis: nucleotide sequence and crucial role in adherence. Proc Natl Acad Sci U S A. 1989 Apr;86(8):2637–2641. doi: 10.1073/pnas.86.8.2637. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Relman D., Tuomanen E., Falkow S., Golenbock D. T., Saukkonen K., Wright S. D. Recognition of a bacterial adhesion by an integrin: macrophage CR3 (alpha M beta 2, CD11b/CD18) binds filamentous hemagglutinin of Bordetella pertussis. Cell. 1990 Jun 29;61(7):1375–1382. doi: 10.1016/0092-8674(90)90701-f. [DOI] [PubMed] [Google Scholar]
- Roberts M., Fairweather N. F., Leininger E., Pickard D., Hewlett E. L., Robinson A., Hayward C., Dougan G., Charles I. G. Construction and characterization of Bordetella pertussis mutants lacking the vir-regulated P.69 outer membrane protein. Mol Microbiol. 1991 Jun;5(6):1393–1404. doi: 10.1111/j.1365-2958.1991.tb00786.x. [DOI] [PubMed] [Google Scholar]
- Rogel A., Hanski E. Distinct steps in the penetration of adenylate cyclase toxin of Bordetella pertussis into sheep erythrocytes. Translocation of the toxin across the membrane. J Biol Chem. 1992 Nov 5;267(31):22599–22605. [PubMed] [Google Scholar]
- Tuomanen E., Towbin H., Rosenfelder G., Braun D., Larson G., Hansson G. C., Hill R. Receptor analogs and monoclonal antibodies that inhibit adherence of Bordetella pertussis to human ciliated respiratory epithelial cells. J Exp Med. 1988 Jul 1;168(1):267–277. doi: 10.1084/jem.168.1.267. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Urisu A., Cowell J. L., Manclark C. R. Involvement of filamentous hemagglutinin in the adherence of Bordetella pertussis to human WiDr cell cultures. Dev Biol Stand. 1985;61:205–214. [PubMed] [Google Scholar]
- Weiss A. A., Goodwin M. S. Lethal infection by Bordetella pertussis mutants in the infant mouse model. Infect Immun. 1989 Dec;57(12):3757–3764. doi: 10.1128/iai.57.12.3757-3764.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Weiss A. A., Hewlett E. L., Myers G. A., Falkow S. Tn5-induced mutations affecting virulence factors of Bordetella pertussis. Infect Immun. 1983 Oct;42(1):33–41. doi: 10.1128/iai.42.1.33-41.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Weiss A. A., Hewlett E. L. Virulence factors of Bordetella pertussis. Annu Rev Microbiol. 1986;40:661–686. doi: 10.1146/annurev.mi.40.100186.003305. [DOI] [PubMed] [Google Scholar]
- Woods D. E., Franklin R., Cryz S. J., Jr, Ganss M., Peppler M., Ewanowich C. Development of a rat model for respiratory infection with Bordetella pertussis. Infect Immun. 1989 Apr;57(4):1018–1024. doi: 10.1128/iai.57.4.1018-1024.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- van't Wout J., Burnette W. N., Mar V. L., Rozdzinski E., Wright S. D., Tuomanen E. I. Role of carbohydrate recognition domains of pertussis toxin in adherence of Bordetella pertussis to human macrophages. Infect Immun. 1992 Aug;60(8):3303–3308. doi: 10.1128/iai.60.8.3303-3308.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]