Medical Protection Against Brucellosis

  • David L. Hoover
  • Richard H. Borschel
Part of the Infectious Disease book series (ID)


Human brucellosis is a systemic, febrile illness caused by at least five different species of Brucella, a Gram-negative, aerobic, nonmotile, nonspore-forming coccobacillus. It has long been considered a prime biowarfare threat agent. As an intracellular parasite of mononuclear phagocytes, it successfully evades many host immune responses and resists easy eradication by antimicrobial agents. These characteristics both increase the need for effective strategies to protect against infection and create challenges to development of vaccines and other antimicrobial countermeasures against the organism.


Colony Form Unit Mononuclear Phagocyte Intracellular Survival Human Brucellosis Brucella Abortus 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    United States Department of the Army. U.S. Army Activity in the United States Biological Warfare Programs, Vols 1 and 2, 24 February 1977 (Unclassified). 1977.Google Scholar
  2. 2.
    National Academy of Sciences (2002) Committees on Biological Warfare. Washington, DC: National Academy of Sciences.Google Scholar
  3. 3.
    Fernandez-Prada, C. M. Nikolich, M., Vemulapalli, R., et al. (2001) Deletion of wboA enhances activation of the lectin pathway of complement in Brucella abortus and Brucella melitensis. Infect Immun. 69(7), 4407–4416.PubMedGoogle Scholar
  4. 4.
    Eze, M. O., Yuan, L., Crawford, R. M., et al. (2000) Effects of opsonization and gamma interferon on growth of Brucella melitensis 16M in mouse peritoneal macrophages in vitro. Infect Immun. 68(1), 257–263.PubMedGoogle Scholar
  5. 5.
    Porte, F., Liautard, J. P., and Kohler, S. (1999) Early acidification of phagosomes containing Brucella suis is essential for intracellular survival in murine macrophages. Infect Immun. 67(8), 4041–4047.PubMedGoogle Scholar
  6. 6.
    Rittig, M. G., Alvarez-Martinez, M. T., Porte, F., Liautard, J. P., and Rouot, B. (2001) Intracellular survival of Brucella spp. in human monocytes involves conventional uptake but special phagosomes. Infect Immun. 69(6), 3995–4006.PubMedGoogle Scholar
  7. 7.
    Naroeni, A., Jouy, N., Ouahrani-Bettache, S., Liautard, J. P., and Porte, F. (2001) Brucella suis-impaired specific recognition of phagosomes by lysosomes due to phagosomal membrane modifications. Infect Immun. 69(1), 486–493.PubMedGoogle Scholar
  8. 8.
    Pizarro-Cerda, J., Moreno, E., Sanguedolce, V., Mege, J. L., and Gorvel, J. P. (1998) Virulent Brucella abortus prevents lysosome fusion and is distributed within autophagosome-like compartments. Infect Immun. 66(5), 2387–2392.PubMedGoogle Scholar
  9. 9.
    Matzinger, P. (2002) The danger model: a renewed sense of self. Science 296(5566), 301–305.PubMedGoogle Scholar
  10. 10.
    Anderson, T. D., Cheville, N. F., and Meador, V. P. (1986) Pathogenesis of placentitis in the goat inoculated with Brucella abortus. II. Ultrastructural studies. Vet. Pathol. 23(3), 227–239.PubMedGoogle Scholar
  11. 11.
    Comerci, D. J., Martinez-Lorenzo, M. J., Sieira, R., Gorvel, J. P., and Ugalde, R. A. (2001) Essential role of the VirB machinery in the maturation of the Brucella abortus-containing vacuole. Cell. Microbiol. 3(3), 159–168.PubMedGoogle Scholar
  12. 12.
    Delrue, R. M., Martinez-Lorenzo, M., Lestrate, P., et al. (2001) Identification of Brucella spp. genes involved in intracellular trafficking. Cell. Microbiol. 3(7), 487–497.PubMedGoogle Scholar
  13. 13.
    Zhan, Y. and Cheers, C. (1993) Endogenous gamma interferon mediates resistance to Brucella abortus infection. Infect. Immun. 61(11), 4899–4901.PubMedGoogle Scholar
  14. 14.
    Murphy, E. A., Sathiyaseelan, J., Parent, M. A., Zou, B., and Baldwin, C. L. (2001) Interferon-gamma is crucial for surviving a Brucella abortus infection in both resistant C57BL/6 and susceptible BALB/c mice. Immunology 103(4), 511–518.PubMedGoogle Scholar
  15. 15.
    Enright, F. M. (1990) The pathogenesis and pathobiology of Brucella infection in domestic animals, in Animal Brucellosis. (Nielsen, K. and Duncan, J. R., eds.), CRC, Boca Raton, FL, pp. 301–320.Google Scholar
  16. 16.
    Spink, W. W. (1950) Clinical aspects of human brucellosis, in Brucellosis. (Larson, C. H. and Soule, M. H., eds.), Waverly, Baltimore, MD, pp. 1–8.Google Scholar
  17. 17.
    Malik, G. M. (1997) A clinical study of brucellosis in adults in the Asir region of southern Saudi Arabia. Am. J. Trop. Med. Hyg. 56(4), 375–377.PubMedGoogle Scholar
  18. 18.
    Mousa, A. R., Muhtaseb, S. A., Almudallal, D. S., Khodeir, S. M., and Marafie, A. A. (1987) Osteoarticular complications of brucellosis: a study of 169 cases. Rev. Infect. Dis. 9(3), 531–543.PubMedGoogle Scholar
  19. 19.
    Gotuzzo, E., Alarcon, G. S., Bocanegra, T. S., et al. (1982) Articular involvement in human brucellosis: a retrospective analysis of 304 cases. Semin. Arthritis Rheum. 12(2), 245–255.PubMedGoogle Scholar
  20. 20.
    Colmenero, J. D., Reguera, J. M., Martos, F., et al. (1996) Complications associated with Brucella melitensis infection: a study of 530 cases. Medicine (Baltimore). 75(4), 195–211.Google Scholar
  21. 21.
    Khan, M. Y., Mah, M. W., and Memish, Z. A. (2001) Brucellosis in pregnant women. Clin. Infect. Dis. 32(8), 1172–1177.PubMedGoogle Scholar
  22. 22.
    Nielsen, K. and Gall, D. (2001) Fluorescence polarization assay for the diagnosis of brucellosis: a review. J. Immunoassay Immunochem. 22(3), 183–201.PubMedGoogle Scholar
  23. 23.
    Yagupsky, P., Peled, N., Press, J., Abramson, O., and Abu, R. M. (1997) Comparison of BACTEC 9240 Peds Plus medium and isolator 1.5 microbial tube for detection of Brucella melitensis from blood cultures. J. Clin. Microbiol. 35(6), 1382–1384.PubMedGoogle Scholar
  24. 24.
    Solera, J., Rodriguez, Z. M., Geijo, P., et al. (1995) Doxycycline-rifampin versus doxycycline-streptomycin in treatment of human brucellosis due to Brucella melitensis. The GECMEI Group. Grupo de Estudio de Castilla-la Mancha de Enfermedades Infecciosas. Antimicrob. Agents Chemother. 39(9), 2061–2067.PubMedGoogle Scholar
  25. 25.
    Madkour, M. M. (2001) Madkour’s Brucellosis. Springer-Verlag. Berlin.Google Scholar
  26. 26.
    (2002) Summary of notifiable diseases—United States, 2000. MMWR Morb Mortal Wkly Rep. 49(53), i–xxii, 1–100.Google Scholar
  27. 27.
    Chomel, B. B., DeBess, E. E., Mangiamele, D. M., et al. (1994) Changing trends in the epidemiology of human brucellosis in California from 1973 to 1992: a shift toward foodborne transmission. J. Infect. Dis. 170(5), 1216–1223.PubMedGoogle Scholar
  28. 28.
    Kaufmann, A. F., Meltzer, M. I., and Schmid, G. P. (1997) The economic impact of a bioterrorist attack: are prevention and postattack intervention programs justifiable? Emerg. Infect. Dis. 3(2), 83–94.PubMedGoogle Scholar
  29. 29.
    Anonymous. (1970) Health Aspects of Chemical and Biological Weapons. World Health Organization, Geneva.Google Scholar
  30. 30.
    Elberg, S. S. and Henderson, D. W. (1948) Respiratory pathogenicity of Brucella. J. Infect. Dis. 82, 302–306.Google Scholar
  31. 31.
    Elberg, S. S., Henderson, D. W., Herzberg, M., and Peacock, S. (1955) Immunization against Brucella infection. IV. Response of monkeys to injection of a streptomycindependent strain of Brucella melitensis. J. Bacteriol. 69, 643–648.PubMedGoogle Scholar
  32. 32.
    Gorelov, V. N., Gubina, E. A., Grekova, N. A., and Skavronskaia, A. G. (1991) [The possibility of creating a vaccinal strain of Brucella abortus 19-BA with multiple antibiotic resistance]. Zh. Mikrobiol. Epidemiol. Immunobiol. 9, 2–4.PubMedGoogle Scholar
  33. 33.
    Crawford, R. M., Van De Verg, L., Yuan, L., et al. (1996) Deletion of purE attenuates Brucella melitensis infection in mice. Infect Immun. 64(6), 2188–2192.PubMedGoogle Scholar
  34. 34.
    Phillips, R. W., Elzer, P. H., Robertson, G. T., et al. (1997) A Brucella melitensis high-temperature-requirement A (htrA) deletion mutant is attenuated in goats and protects against abortion. Res. Vet. Sci. 63(2), 165–167.PubMedGoogle Scholar
  35. 35.
    Elzer, P. H., Phillips, R. W., Kovach, M. E., Peterson, K. M., Roop, R. n. (1994) Characterization and genetic complementation of a Brucella abortus high-temperature-requirement A (htrA) deletion mutant. Infect. Immun. 62(10), 4135–4139.PubMedGoogle Scholar
  36. 36.
    Elzer, P. H., Enright, F. M., McQuiston, J. R., Boyle, S. M., and Schurig, G. G. (1998) Evaluation of a rough mutant of Brucella melitensis in pregnant goats. Res. Vet. Sci. 64(3), 259, 260.PubMedGoogle Scholar
  37. 37.
    Edmonds, M., Booth, N., Hagius, S., et al. (2000) Attenuation and immunogenicity of a Brucella abortus htrA cycL double mutant in cattle. Vet. Microbiol. 76(1), 81–90.PubMedGoogle Scholar
  38. 38.
    Cheville, N. F., Olsen, S. C., Jensen, A. E., et al. (1996) Bacterial persistence and immunity in goats vaccinated with a purE deletion mutant or the parental 16M strain of Brucella melitensis. Infect. Immun. 64(7), 2431–2439.PubMedGoogle Scholar
  39. 39.
    Meador, V. P. and Deyoe, B. L. (1986) Experimentally induced Brucella abortus infection in pregnant goats. Am. J. Vet. Res. 47(11), 2337–2342.PubMedGoogle Scholar
  40. 40.
    Corner, L. A., Alton, G. G., Iyer, H. (1987) Distribution of Brucella abortus in infected cattle. Aust. Vet. J. 64(8), 241–244.PubMedGoogle Scholar
  41. 41.
    Fensterbank, R., Pardon, P., and Marly, J. (1985) Vaccination of ewes by a single conjunctival administration of Brucella melitensis Rev. 1 vaccine. Ann. Rech. Vet. 16(4), 351–356.PubMedGoogle Scholar
  42. 42.
    Nicoletti, P. and Milward, F. W. (1983) Protection by oral administration of brucella abortus strain 19 against an oral challenge exposure with a pathogenic strain of Brucella. Am. J. Vet. Res. 44(9), 1641–1643.PubMedGoogle Scholar
  43. 43.
    Plommet, M. and Plommet, A. M. (1975) Vaccination against bovine brucellosis with a low dose of strain 19 administered by the conjunctival route. I.—Protection demonstrated in guinea pigs. Ann. Rech. Vet. 6(4), 345–356.PubMedGoogle Scholar
  44. 44.
    Fensterbank, R., Pardon, P., and Marly, J. (1982) Efficacy of Brucella melitensis Rev. 1 vaccine against Brucella ovis infection in rams. Ann. Rech. Vet. 13(2), 185–190.PubMedGoogle Scholar
  45. 45.
    Corbel, M. J., Morris, J. A., Thorns, C. J., and Redwood, D. W. (1983) Response of the badger (Meles meles) to infection with Brucella abortus. Res. Vet. Sci. 34(3), 296–300.PubMedGoogle Scholar
  46. 46.
    Carmichael, L. E., Zoha, S. J., and Flores-Castro, R. (1984) Biological properties and dog response to a variant (M-) strain of Brucella canis. Dev. Biol. Stand. 56, 649–656.PubMedGoogle Scholar
  47. 47.
    Pardon, P. and Marly, J. (1976) Resistance of Brucella abortus infected mice to intravenous or intraperitoneal Brucella reinfection. Ann. Immunol. (Paris) 127(1), 57–70.Google Scholar
  48. 48.
    Pardon, P. and Marly, J. (1976) Killed vaccine in adjuvant and protection of mice against an intraperitoneal challenge of Brucella: kinetic studies. Ann. Rech. Vet. 7(4), 297–305.PubMedGoogle Scholar
  49. 49.
    Montaraz, J. A. and Winter, A. J. (1986) Comparison of living and nonliving vaccines for Brucella abortus in BALB/c mice. Infect. Immun. 53(2), 245–251.PubMedGoogle Scholar
  50. 50.
    Dubray, G. and Bezard, G. (1980) Isolation of three Brucella abortus cell-wall antigens protective in murine experimental brucellosis. Ann. Rech. Vet. 11(4), 367–373.PubMedGoogle Scholar
  51. 51.
    Jacques, I., Olivier, B. V., and Dubray, G. (1991) Induction of antibody and protective responses in mice by Brucella O-polysaccharide-BSA conjugate. Vaccine 9(12), 896–900.PubMedGoogle Scholar
  52. 52.
    Phillips, M., Deyoe, B. L., and Canning, P. C. (1989) Protection of mice against Brucella abortus infection by inoculation with monoclonal antibodies recognizing Brucella Oantigen. Am. J. Vet. Res. 50, 2158–2161.PubMedGoogle Scholar
  53. 53.
    Plommet, M. and Plommet, A. M. (1989) Immunity to Brucella abortus induced in mice by popliteal lymph node restricted strain 19 vaccination. Ann. Rech. Vet. 20(1), 73–81.PubMedGoogle Scholar
  54. 54.
    Tabatabai, L. B., Pugh, G. J., Stevens, M. G., Phillips, M., and McDonald, T. J. (1992) Monophosphoryl lipid A-induced immune enhancement of Brucella abortus salt-extractable protein and lipopolysaccharide vaccines in BALB/c mice. Am. J. Vet. Res. 53(10), 1900–1907.PubMedGoogle Scholar
  55. 55.
    Pugh, G. J., Tabatabai, L. B., Bricker, B. J., et al. (1990) Immunogenicity of Brucella-extracted and recombinant protein vaccines in CD-1 and BALB/c mice. Am. J. Vet. Res. 51(9), 1413–1420.PubMedGoogle Scholar
  56. 56.
    Limet, J., Plommet, A. M., Dubray, G., and Plommet, M. (1987) Immunity conferred upon mice by anti-LPS monoclonal antibodies in murine brucellosis. Ann. Inst. Pasteur Immunol. 138(3), 417–424.PubMedGoogle Scholar
  57. 57.
    Montaraz, J. A., Winter, A. J., Hunter, D. M., Sowa, B. A., Wu, A. M., and Adams, L. G. (1986) Protection against Brucella abortus in mice with O-polysaccharide-specific monoclonal antibodies. Infect. Immun. 51(3), 961–963.PubMedGoogle Scholar
  58. 58.
    Jacques, I., Cloeckaert, A., Limet, J. N., and Dubray, G. (1992) Protection conferred on mice by combinations of monoclonal antibodies directed against outer-membrane proteins or smooth lipopolysaccharide of Brucella. J. Med. Microbiol. 37(2), 100–103.PubMedGoogle Scholar
  59. 59.
    Bowden, R. A., Cloeckaert, A., Zygmunt, M. S., and Dubray, G. (1995) Outer-membrane protein-and rough lipopolysaccharide-specific monoclonal antibodies protect mice against Brucella ovis. J. Med. Microbiol. 43(5), 344–347.PubMedGoogle Scholar
  60. 60.
    Sulitzeanu, D. (1959) The fate of killed, radioiodinated Brucella abortus injected into mice. J. Immunol. 82, 304–312.PubMedGoogle Scholar
  61. 61.
    Sulitzeanu, D. (1965) Mechanism of immunity against Brucella. Nature 205, 1086–1088.PubMedGoogle Scholar
  62. 62.
    Pardon, P. (1977) Resistance against a subcutaneous Brucella challenge of mice immunized with living or dead Brucella or by transfer of immune serum. Ann. Immunol. (Paris) 128(6), 1025–1037.Google Scholar
  63. 63.
    Pardon, P. and Marly, J. (1978) Resistance of normal or immunized guinea pigs against a subcutaneous challenge of Brucella abortus. Ann. Rech. Vet. 9(3), 419–425.PubMedGoogle Scholar
  64. 64.
    Jones, S. M. and Winter, A. J. (1992) Survival of virulent and attenuated strains of Brucella abortus in normal and gamma interferon-activated murine peritoneal macrophages. Infect. Immun. 60(7), 3011–3014.PubMedGoogle Scholar
  65. 65.
    Gross, A., Spiesser, S., Terraza, A., Rouot, B., Caron, E., and Dornand, J. (1998) Expression and bactericidal activity of nitric oxide synthase in Brucella suis-infected murine macrophages. Infect. Immun. 66(4), 1309–1316.PubMedGoogle Scholar
  66. 66.
    Pavlov, H., Hogarth, M., McKenzie, I. F., and Cheers, C. (1982) In vivo and in vitro effects of monoclonal antibody to Ly antigens on immunity to infection. Cell. Immunol. 71(1), 127–138.PubMedGoogle Scholar
  67. 67.
    Araya, L. N., Elzer, P. H., Rowe, G. E., Enright, F. M., and Winter, A. J. (1989) Temporal development of protective cell-mediated and humoral immunity in BALB/c mice infected with Brucella abortus. J. Immunol. 143(10), 3330–3337.PubMedGoogle Scholar
  68. 68.
    Plommet, M., Hue, I., and Plommet, A. M. (1986) [Anti-Brucella immunity transferred by immune serum and that transferred by splenic lymphocytes cannot be added]. Ann. Rech. Vet. 16(2), 169–175.Google Scholar
  69. 69.
    Araya, L. N. and Winter, A. J. (1990) Comparative protection of mice against virulent and attenuated strains of Brucella abortus by passive transfer of immune T cells or serum. Infect. Immun. 58(1), 254–256.PubMedGoogle Scholar
  70. 70.
    Nicoletti, P. (1990) Vaccination, in Animal Brucellosis. (Nielsen, K. and Duncan, J. R., eds.), CRC, Boca Raton, FL, pp. 283–300.Google Scholar
  71. 71.
    Kaneene, J. M., Anderson, R. K., Johnson, D. W., et al. (1978) Whole-blood lymphocyte stimulation assay for measurement of cell-mediated immune responses in bovine brucellosis. J. Clin. Microbiol. 7(6), 550–557.PubMedGoogle Scholar
  72. 72.
    Stevens, M. G., Olsen, S. C., and Cheville, N. F. (1996) Lymphocyte proliferation in response to Brucella abortus RB51 and 2308 proteins in RB51-vaccinated or 2308-infected cattle. Infect. Immun. 64(3), 1007–1010.PubMedGoogle Scholar
  73. 73.
    Cloeckaert, A., Zygmunt, M. S., and Guilloteau, L. A. (2002) Brucella abortus vaccine strain RB51 produces low levels of M-like O-antigen. Vaccine 20(13), 1820–1822.PubMedGoogle Scholar
  74. 74.
    Vemulapalli, R., He, Y., Buccolo, L. S., Boyle, S. M., Sriranganathan, N., and Schurig, G. G. (2000) Complementation of Brucella abortus RB51 with a functional wboA gene results in O-antigen synthesis and enhanced vaccine efficacy but no change in rough phenotype and attenuation. Infect. Immun. 68(7), 3927–3932.PubMedGoogle Scholar
  75. 75.
    Winter, A. J., Schurig, G. G., Boyle, S. M., et al. (1996) Protection of BALB/c mice against homologous and heterologous species of Brucella by rough strain vaccines derived from Brucella melitensis and Brucella suis biovar 4. Am. J. Vet. Res. 57(5), 677–683.PubMedGoogle Scholar
  76. 76.
    Elberg, S. S. and Silverman, S. J. Immunology of Brucellosis, in Brucellosis. (Larson, C. H. and Soule, M. H., eds.), Waverly, Baltimore, MD, pp. 62–84.Google Scholar
  77. 77.
    Hadjichristodoulou, C., Voulgaris, P., Toulieres, L., et al. (1994) Tolerance of the human brucellosis vaccine and the intradermal reaction test for brucellosis. Eur. J. Clin. Microbiol. Infect. Dis. 13(2), 129–134.PubMedGoogle Scholar
  78. 78.
    Bentejac, M. C., Biron, G., Bertrand, A., and Bascoul, S. (1984) [Vaccination against human brucellosis. 2 years of experience]. Dev. Biol. Stand. 56, 531–535.PubMedGoogle Scholar
  79. 79.
    Bascoul, S., Peraldi, M., Merino, A. L., Lacave, C., Cannat, A., and Serre, A. (1976) Stimulating activity of Brucella fractions in a human lymphocyte transformation test. Correlation with humoral and cellular immunity. Immunology 31(5), 717–722.PubMedGoogle Scholar
  80. 80.
    Sulitzeanu, D. (1955) Passive protection experiments with Brucella antisera. J. Hygiene. 53, 133–142.Google Scholar
  81. 81.
    Elberg, S. S. (1973) Immunity to brucella infection. Medicine (Baltimore) 52(4), 339–356.Google Scholar
  82. 82.
    Spink, W. W., Hall, J. W. I., Finstad, J., and Mallet, E. (1962) Immunization with viable Brucella organisms. Results of a safety test in humans. Bull. WHO 26, 409–419.PubMedGoogle Scholar
  83. 83.
    Aleksandrov, N. I., Gefen, N. Y., Garin, N. S., Gapochko, K. G., Daal-Berg, I. I., and Sergeyev, V. M. (1958) Reactogenicity and effectiveness of aerogenic vaccination against certain zoonoses. Voenno-Meditsinskii (USSR) 12, 51–59.Google Scholar
  84. 84.
    Aleksandrov, N. I., Gefen, N. Y., Gapochko, K. G., Garin, N. S., Maslov, A. I., and Mishchenko, V. V. (1962) A clinical study of postvaccinal reactions to aerosol immunization with powdered brucellosis vaccines. Zhurnal. Mikrobiologii. 33, 31–37.Google Scholar
  85. 85.
    Elberg, S. S., ed. (1981) A Guide to the Diagnosis, Treatment and Prevention of Human Brucellosis. World Health Organization, Geneva.Google Scholar
  86. 86.
    Pappagianis, D., Elberg, S. S., and Crouch, D. (1966) Immunization against Brucella infections. Effects of graded doses of viable attenuated Brucella melitensis in humans. Am. J. Epidemiol. 84, 21–31.PubMedGoogle Scholar
  87. 87.
    Shaw, E. A. (1907) Immunity, serum, toxin, and vaccine experiments on monkeys with regard to Mediterranean Fever. Mediterranean Fever Commission of the Royal Society (Great Britain); Part V.Google Scholar
  88. 88.
    Fleischner, E. C. and Meyer, K. F. (1920) Preliminary observations on the pathogenicity for monkeys of the Bacillus abortus bovinus. Trans. Am. Pediatr. Soc. 32, 141–145.Google Scholar
  89. 89.
    Huddleson, I. F. and Hallman, E. T. (1929) The pathogenicity of the species of the genus Brucella for monkeys. J. Infect. Dis. 45, 293–303.Google Scholar
  90. 90.
    Henderson, D. W. (1952) An apparatus for the study of airborne infection. J. Hygiene. 50, 53–68.Google Scholar
  91. 91.
    Kruse, R. H. and Wedum, A. G. (1970) Cross infection with eighteen pathogens among caged laboratory animals. Lab. Anim. Care. 20(3), 541–560.PubMedGoogle Scholar
  92. 92.
    Rosebury, T. (1947) Experimental Air-Borne Infection. Williams and Wilkins, Baltimore, MD.Google Scholar
  93. 93.
    Herzberg, M. aand Elberg, S. (1953) Immunization against Brucella infection. I. Isolation and characterization of a streptomycin-dependent mutant. J. Bacteriol. 66, 585–599.PubMedGoogle Scholar
  94. 94.
    Herzberg, M., Elberg, S. S., and Meyer, K. F. (1953) Immunization against Brucella infection. II. Effectiveness of a streptomycin-dependent strain of Brucella melitensis. J. Bacteriol. 66, 600–605.PubMedGoogle Scholar
  95. 95.
    Herzberg, M. and Elberg, S. S. (1955) Immunization against Brucella infection. III. Response of mice and guinea pigs to injection of viable and nonviable suspensions of a streptomycin-dependent mutant of Brucella melitensis. J. Bacteriol. 69, 432–435.PubMedGoogle Scholar
  96. 96.
    Elberg, S. S. and Meyer, K. F. (1958) Caprine immunization against brucellosis. Bull. WHO 19, 711–724.PubMedGoogle Scholar
  97. 97.
    Elberg, S. S. and Faunce, W. K. (1962) Immunization against Brucella infection. 8. The response of Cynomolgus phillipinensis, guinea-pigs and pregnant goats to infection by the Rev I strain of Brucella melitensis. Bull. WHO 26, 421–436.PubMedGoogle Scholar
  98. 98.
    Chen, T. H. and Elberg, S. S. (1970) Immunization against Brucella infections: immune response of mice, guinea pigs, and Cynomolgus philipinensis to live and killed Brucella melitensis strain Rev. I administered by various methods. J. Infect. Dis. 122(6), 489–500.PubMedGoogle Scholar
  99. 99.
    Chen, T. H. and Elberg, S. S. (1973) Immunization against Brucella infections. Priming of Cynomolgus philipinensis with purified antigen of Brucella melitensis prior to injection of Rev. I vaccine. J. Comp. Pathol. 83(3), 357–367.PubMedGoogle Scholar
  100. 100.
    Mense, M. G., Van De Verg, L. L., Bhattacharjee, A. K., et al. (2001) Bacteriologic and histologic features in mice after intranasal inoculation of Brucella melitensis. Am. J. Vet. Res. 62(3), 398–405.PubMedGoogle Scholar
  101. 101.
    Drazek, E. S., Houng, H. S., Crawford, R. M., Hadfield, T. L., Hoover, D. L., and Warren, R. L. (1995) Deletion of purE attenuates Brucella melitensis 16M for growth in human monocyte-derived macrophages. Infect. Immun. 63(9), 3297–3301.PubMedGoogle Scholar
  102. 102.
    Hoover, D. L., Crawford, R. M., Van De Verg, L. L., et al. (1999) Protection of mice against brucellosis by vaccination with Brucella melitensis WR201(16MDeltapurEK). Infect. Immun. 67(11), 5877–5884.PubMedGoogle Scholar
  103. 103.
    Van De Verg, L. L., Hartman, A. B., Bhattacharjee, A. K., et al. (1996) Outer membrane protein of Neisseria meningitidis as a mucosal adjuvant for lipopolysaccharide of Brucella melitensis in mouse and guinea pig intranasal immunization models. Infect. Immun. 64(12), 5263–5268.Google Scholar
  104. 104.
    Bhattacharjee, A. K., Van de Verg, L., Izadjoo, M. J., et al. (2002) Protection of mice against brucellosis by intranasal immunization with Brucella melitensis lipopolysaccharide as a noncovalent complex with Neisseria meningitidis group B outer membrane protein. Infect. Immun. 70(7), 3324–3329.PubMedGoogle Scholar
  105. 105.
    Formal, S. B., Gemski, P., Baron, L. S., and LaBrec, E. H. (1971) A Chromosomal Locus Which Controls the Ability of Shigella flexneri to Evoke Keratoconjunctivitis. Infect. Immun. 3(1), 73–79.PubMedGoogle Scholar
  106. 106.
    McFarland, W. C. and Stocker, B. A. (1987) Effect of different purine auxotrophic mutations on mouse-virulence of a Vi-positive strain of Salmonella dublin and of two strains of Salmonella typhimurium. Microb. Pathog. 3(2), 129–141.PubMedGoogle Scholar
  107. 107.
    Foulongne, V., Bourg, G., Cazevieille, C., Michaux-Charachon, S., and O’Callaghan, D. (2000) Identification of Brucella suis genes affecting intracellular survival in an in vitro human macrophage infection model by signature-tagged transposon mutagenesis. Infect. Immun. 68(3), 1297–1303.PubMedGoogle Scholar
  108. 108.
    Hong, P. C., Tsolis, R. M., and Ficht, T. A. (2000) Identification of Genes Required for Chronic Persistence of Brucella abortus in Mice. Infect. Immun. 68(7), 4102–4107.PubMedGoogle Scholar
  109. 109.
    Lestrate, P., Delrue, R. M., Danese, I., et al. (2000) Identification and characterization of in vivo attenuated mutants of Brucella melitensis. Mol. Microbiol. 38(3), 543–551.PubMedGoogle Scholar
  110. 110.
    DelVecchio, V. G., Kapatral, V., Redkar, R. J., et al. (2002) The genome sequence of the facultative intracellular pathogen Brucella melitensis. Proc. Natl. Acad. Sci. USA 99(1), 443–448.PubMedGoogle Scholar
  111. 111.
    Paulsen, I. T., Seshadri, R., Nelson, K. E., et al. (2002) The Brucella suis genome reveals fundamental similarities between animal and plant pathogens and symbionts. Proc. Natl. Acad. Sci. USA 99(20), 13,148–13,153.PubMedGoogle Scholar
  112. 112.
    Tatum, F. M., Cheville, N. F., and Morfitt, D. (1994) Cloning, characterization and construction of htrA and htrA-like mutants of Brucella abortus and their survival in BALB/c mice. Microb. Pathog. 17(1), 23–36.PubMedGoogle Scholar
  113. 113.
    Roop, R. M., 2nd, Phillips, R. W., Hagius, S., et al. (2001) Re-examination of the role of the Brucella melitensis HtrA stress response protease in virulence in pregnant goats. Vet. Microbiol. 82(1), 91–95.PubMedGoogle Scholar
  114. 114.
    Phillips, R. W. and Roop, R. M., 2nd. (2001) Brucella abortus HtrA functions as an authentic stress response protease but is not required for wild-type virulence in BALB/c mice. Infect. Immun. 69(9), 5911–5913.PubMedGoogle Scholar
  115. 115.
    Alvarez-Martinez, M. T., Machold, J., Weise, C., Schmidt-Eisenlohr, H., Baron, C., and Rouot, B. (2001) The Brucella suis homologue of the Agrobacterium tumefaciens chromosomal virulence operon chvE is essential for sugar utilization but not for survival in macrophages. J. Bacteriol. 183(18), 5343–5351.PubMedGoogle Scholar
  116. 116.
    Boschiroli, M. L., Cravero, S. L., Arese, A. I., Campos, E., and Rossetti, O. L. (1997) Protection against infection in mice vaccinated with a Brucella abortus mutant. Infect. Immun. 65(2), 798–800.PubMedGoogle Scholar
  117. 117.
    Denoel, P. A., Crawford, R. M., Zygmunt, M. S., et al. (1997) Survival of a bacterioferritin deletion mutant of Brucella melitensis 16M in human monocyte-derived macrophages. Infect. Immun. 65(10), 4337–4340.PubMedGoogle Scholar
  118. 118.
    Dorrell, N., Spencer, S., Foulonge, V., Guigue, T. P., O’Callaghan, D., and Wren, B. W. (1998) Identification, cloning and initial characterisation of FeuPQ in Brucella suis: a new sub-family of two-component regulatory systems. FEMS Microbiol. Lett. 162(1), 143–150.PubMedGoogle Scholar
  119. 119.
    Sangari, F. J., Grillo, M. J., Jimenez De Bagues, M. P., et al. (1998) The defect in the metabolism of erythritol of the Brucella abortus B19 vaccine strain is unrelated with its attenuated virulence in mice. Vaccine 16(17), 1640–1645.PubMedGoogle Scholar
  120. 120.
    Tibor, A., Jacques, I., Guilloteau, L., et al. (1998) Effect of P39 gene deletion in live Brucella vaccine strains on residual virulence and protective activity in mice. Infect. Immun. 66(11), 5561–5564.PubMedGoogle Scholar
  121. 121.
    Bellaire, B. H., Elzer, P. H., Baldwin, C. L., Roop, R. M., 2nd. (1999) The siderophore 2,3-dihydroxybenzoic acid is not required for virulence of Brucella abortus in BALB/c mice. Infect. Immun. 67(5), 2615–2618.PubMedGoogle Scholar
  122. 122.
    Dorrell, N., Guigue-Talet, P., Spencer, S., Foulonge, V., O’Callaghan, D., and Wren, B. W. (1999) Investigation into the role of the response regulator NtrC in the metabolism and virulence of Brucella suis. Microb. Pathog. 27(1), 1–11.PubMedGoogle Scholar
  123. 123.
    Petrovska, L., Hewinson, R. G., Dougan, G., Maskell, D. J., and Woodward, M. J. (1999) Brucella melitensis 16M: characterisation of the galE gene and mouse immunisation studies with a galE deficient mutant. Vet. Microbiol. 65(1), 21–36.PubMedGoogle Scholar
  124. 124.
    Ko, J. and Splitter, G. A. (2000) Residual virulence of Brucella abortus in the absence of the cytochrome bc(1)complex in a murine model in vitro and in vivo. Microb. Pathog. 29(3), 191–200.PubMedGoogle Scholar
  125. 125.
    Ko, J. and Splitter, G. A. (2000) Brucella abortus tandem repeated ATP-binding proteins, BapA and BapB, homologs of haemophilus influenzae LktB, are not necessary for intracellular survival. Microb. Pathog. 29(4), 245–253.PubMedGoogle Scholar
  126. 126.
    Robertson, G. T., Kovach, M. E., Allen, C. A., Ficht, T. A., and Roop, R. M., 2nd. (2000) The Brucella abortus Lon functions as a generalized stress response protease and is required for wild-type virulence in BALB/c mice. Mol. Microbiol. 35(3), 577–588.PubMedGoogle Scholar
  127. 127.
    Ekaza, E., Guilloteau, L., Teyssier, J., Liautard, J. P., and Kohler, S. (2000) Functional analysis of the ClpATPase ClpA of Brucella suis, and persistence of a knockout mutant in BALB/c mice. Microbiology 146(Pt 7), 1605–1616.PubMedGoogle Scholar
  128. 128.
    McQuiston, J. R., Vemulapalli, R., Inzana, T. J., et al. (1999) Genetic characterization of a Tn5-disrupted glycosyltransferase gene homolog in Brucella abortus and its effect on lipopolysaccharide composition and virulence. Infect. Immun. 67(8), 3830–3835.PubMedGoogle Scholar
  129. 129.
    Godfroid, F., Taminiau, B., Danese, I., et al. (1998) Identification of the perosamine synthetase gene of Brucella melitensis 16M and involvement of lipopolysaccharide O side chain in Brucella survival in mice and in macrophages. Infect. Immun. 66(11), 5485–5493.PubMedGoogle Scholar
  130. 130.
    Allen, C. A., Adams, L. G., and Ficht, T. A. (1998) Transposon-derived Brucella abortus rough mutants are attenuated and exhibit reduced intracellular survival. Infect. Immun. 66(3), 1008–1016.PubMedGoogle Scholar
  131. 131.
    Ugalde, J. E., Czibener, C., Feldman, M. F., and Ugalde, R. A. (2000) Identification and characterization of the Brucella abortus phosphoglucomutase gene: role of lipopolysaccharide in virulence and intracellular multiplication. Infect. Immun. 68(10), 5716–5723.PubMedGoogle Scholar
  132. 132.
    Foulongne, V., Walravens, K., Bourg, G., et al. (2001) Aromatic compound-dependent Brucella suis is attenuated in both cultured cells and mouse models. Infect. Immun. 69(1), 547–550.PubMedGoogle Scholar
  133. 133.
    Watarai, M., Makino, S., and Shirahata, T. (2002) An essential virulence protein of Brucella abortus, VirB4, requires an intact nucleoside-triphosphate-binding domain. Microbiology 148(Pt 5), 1439–1446.PubMedGoogle Scholar
  134. 134.
    O’Callaghan, D., Cazevieille, C., Allardet-Servent, A., et al. (1999) A homologue of the Agrobacterium tumefaciens VirB and Bordetella pertussis Ptl type IV secretion systems is essential for intracellular survival of Brucella suis. Mol. Microbiol. 33(6), 1210–1220.PubMedGoogle Scholar
  135. 135.
    Sieira, R., Comerci, D. J., Sanchez, D. O., and Ugalde, R. A. (2000) A homologue of an operon required for DNA transfer in Agrobacterium is required in Brucella abortus for virulence and intracellular multiplication. J. Bacteriol. 182(17), 4849–4855.PubMedGoogle Scholar
  136. 136.
    Kohler, S., Teyssier, J., Cloeckaert, A., Rouot, B., and Liautard, J. P. (1996) Participation of the molecular chaperone DnaK in intracellular growth of Brucella suis within U937-derived phagocytes. Mol. Microbiol. 20(4), 701–712.PubMedGoogle Scholar
  137. 137.
    Kohler, S., Ekaza, E., Paquet, J. Y., et al. (2002) Induction of dnaK through its native heat shock promoter is necessary for intramacrophagic replication of Brucella suis. Infect. Immun. 70(3), 1631–1634.PubMedGoogle Scholar
  138. 138.
    LeVier, K., Phillips, R. W., Grippe, V. K., Roop, R. M., 2nd, and Walker, G. C. (2000) Similar requirements of a plant symbiont and a mammalian pathogen for prolonged intracellular survival. Science 287(5462), 2492–2493.PubMedGoogle Scholar
  139. 139.
    Inon de Iannino, N., Briones, G., Tolmasky, M., and Ugalde, R. A. (1998) Molecular cloning and characterization of cgs, the Brucella abortus cyclic beta(1–2) glucan synthetase gene: genetic complementation of Rhizobium meliloti ndvB and Agrobacterium tumefaciens chvB mutants. J. Bacteriol. 180(17), 4392–4400.PubMedGoogle Scholar
  140. 140.
    Briones, G., Inon de Iannino, N., Roset, M., Vigliocco, A., Paulo, P. S., and Ugalde, R. A. (2001) Brucella abortus cyclic beta-1,2-glucan mutants have reduced virulence in mice and are defective in intracellular replication in HeLa cells. Infect. Immun. 69(7), 4528–4535.PubMedGoogle Scholar
  141. 141.
    Sola-Landa, A., Pizarro-Cerda, J., Grillo, M. J., et al. (1998) A two-component regulatory system playing a critical role in plant pathogens and endosymbionts is present in Brucella abortus and controls cell invasion and virulence. Mol. Microbiol. 29(1), 125–138.PubMedGoogle Scholar
  142. 142.
    Robertson, G. T. and Roop, R. (1999) The Brucella abortus host factor I (HF-I) protein contributes to stress resistance during stationary phase and is a major determinant of virulence in mice. Mol. Microbiol. 34(4), 690–700.PubMedGoogle Scholar
  143. 143.
    Almiron, M., Martinez, M., Sanjuan, N., and Ugalde, R. A. (2001) Ferrochelatase is present in Brucella abortus and is critical for its intracellular survival and virulence. Infect. Immun. 69(10), 6225–6230.PubMedGoogle Scholar
  144. 144.
    Elzer, P. H., Phillips, R. W., Robertson, G. T., and Roop, R. n. (1996) The HtrA stress response protease contributes to resistance of Brucella abortus to killing by murine phagocytes. Infect. Immun. 64(11), 4838–4841.PubMedGoogle Scholar
  145. 145.
    Elzer, P. H., Hagius, S. D., Robertson, G. T., et al. (1996) Behaviour of a high-temperature-requirement A (HtrA) deletion mutant of Brucella abortus in goats. Res. Vet. Sci. 60(1), 48–50.PubMedGoogle Scholar
  146. 146.
    Phillips, R. W., Elzer, P. H., and Roop, R. I. (1995) A Brucella melitensis high temperature requirement A (htrA) deletion mutant demonstrates a stress response defective phenotype in vitro and transient attenuation in the BALB/c mouse model. Microb. Pathog. 19(5), 227–284.PubMedGoogle Scholar
  147. 147.
    Edmonds, M. D., Cloeckaert, A., Booth, N. J., et al. (2001) Attenuation of a Brucella abortus mutant lacking a major 25 kDa outer membrane protein in cattle. Am. J. Vet. Res. 62(9), 1461–1466.PubMedGoogle Scholar

Copyright information

© Humana Press Inc., Totowa, NJ 2005

Authors and Affiliations

  • David L. Hoover
    • 1
  • Richard H. Borschel
    • 1
  1. 1.Department of Bacterial DiseasesWalter Reed Army Institute of ResearchSilver Spring

Personalised recommendations