Abstract
Brucellosis is a zoonostic disease caused by Gram negative Brucella species bacteria. B. melitensis, B. abortus and B. suis cause third trimester abortions in sheep and goats, cattle and swine, respectively. Serological diagnosis, in the past century, was based upon measurements of agglutinins and complement fixing antibodies while current state of art techniques include ELISA and fluorescence polarization. Our data show that following abortion or normal parturition, Brucella are secreted in the milk of lactating animals prior to development of a detectable humoral response, thereby reducing the reliability of serological diagnosis as the cornerstone of eradication programs. Accordingly, we hypothesized that infection starts as a clandestine invasion of the host by Brucella where, by some as yet unrecognized mechanism, the organisms manage to evade the immune response. Pregnancy then exerts physiological changes on the brucellae organisms that activate their virulence properties, allowing invasion and colonization of the trophoblasts in the third trimester, causing abortion and spread of the organisms to the external environment. Changes in the virulence properties of the bacteria within the blood stream also trigger their invasion of and propagation in the mammary glands, sustaining their secretion in the milk. These dual characteristics of Brucella’s stealth invasion of the host on one hand, and escape via abortive or secretion pathways on the other, demonstrate a unique virulence pattern specifically attainable due to the synchronization of their life cycle to the animal’s gestation cycle.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsReferences
Alexander, B., Schnurrenberger P. R. & Brown R. R. (1981) Numbers of Brucella abortus in the placenta, umbilicus and fetal fluid of two naturally infected cows. Vet Rec, 108, 500.
Alton, G. G. & Corner, L. A. (1981) Vaccination of heifers with a reduced dose of Brucella abortus strain 19 vaccine before first mating. Aust Vet J, 57, 548–50.
Alton, G. G., Jones, L. M., Angus, R. D. & Verger, J. M. (1988) Techniques for the brucellosis laboratory. Institut National De La Recherche Agronomique, Paris.
Banai, M. (2002) Control of small ruminant brucellosis by use of Brucella melitensis Rev.1 vaccine: laboratory aspects and field applications. Vet Micobiol, 90, 497–519.
Barqueiro-Calvo, E., Chaves-Olarte, E., Weiss, D. S., Guzmán-Verri, C., Chacon-Diaz, A., Rucavado, A., Moriyon, I. & Moreno, E. (2007) Brucella abortus uses a stealthy strategy to avoid activation of the innate immune system during the onset of infection. PLoS ONE 2(7), e631.
Barqueiro-Calvo, E., Conde-Alvarez, R., Chacón-Diaz, C., Quesada-Lobo, L., Martirosyan, A., Guzmán-Verri, C., Iriarte, M., Mancek-Keber, M., Jeral, R., Gorvel, J. -P., Moriyón, I, Moreno, E. & Chaves-Olarte, E. (2009) The differential interaction of Brucella and Ochrobactrum with innate immunity reveals traits related to the evolution of stealthy pathogens. PLoS ONE 4(6), e5893.
Buck, J. M. (1930) Studies of vaccination during calfhood to prevent bovine infectious abortion. J Agricul Res, 41, 667-89.
Cardoso, P. G., Macedo, G. C., Azevedo, V. & Oliveira, S. C. (2006) Brucella spp. noncanonical LPS: structure, biosynthesis, and interaction with host immune system. Microbial Cell Fact, 5, 13.
Celli, J. & Gorvel, J. -P. (2004) Organelle roberry: Brucella interactions with the endoplasmic reticulum. Curr Opin Microbiol., 7, 93–7.
Chain, P. S. G., Comerci, D. J., Tolmasky, M. E., Larimer, F. W., Malfatti, S. A., Vergez, L. M., Aguero, F., Land, M. L., Ugalde, R. A. & Garcia, E. (2005) Whole-genome analyses of speciation events in pathogenic Brucellae Infect Immun, 73, 8353–61.
Corbel, M. J. (1997) Brucellosis: an overview. Emerg Infect Dis, 3, 213–21.
Delvecchio, V. G., Kapatral, V., Redkar, R. J., Patra, G., Mujer, C., Los, T., Ivanova, N., Anderson, I., Bhattacharyya, A., Lykidis, A., Reznik, G., Jablonski, L., Larsen, N., D’souza, M., Bernal, A., Mazur, M., Goltsman, E., Selkov, E., Elzer, P. H., Hagius, S., O’callaghan, D., Letesson, J. J., Haselkorn, R., Kyrpides, N. & Overbeek, R. (2002) The genome sequence of the facultative intracellular pathogen Brucella melitensis. Proc Natl Acad Sci USA, 99, 443–8.
Fensterbank, R., Pardon, P. & Marly, J. (1985) Vaccination of ewes by a single conjuctival administration of Brucella melitensis Rev. 1 vaccine. Ann Rech Vet, 16, 351–6.
Foster, J. T., Beckstrom-Sternberg, S. M., Pearson, T., Beckstrom-Sternberg, J. S., Chain, P. S. G., Roberto, F. F., Hnath, J., Brettin, T. & Keim, P. (2009) Whole-genome-based phylogeny and divergence of the genus Brucella J Bacteriol, 191, 2864–70.
Foster, G., Osterman, B. J., Godfroid, J., Jacques, I. & Cloeckaert, A. (2007) Brucella ceti sp. nov. and Brucella pinnipedialis sp. nov. for Brucella strains with cetaceans and seals as their preferred hosts. Intl J Sys Evol Microbiol, 57, 2688–93.
Gall, D. & Nielsen, K. (2004) Serological diagnosis of bovine brucellosis: a review of test performance and cost comparison. Revue Scientifique et Technique (The Office International des Epizooties, Paris) 23, 989–1002.
Goldstein, J., Hoffman, T., Frasch, C., Lizzio, E. F., Beining, P. R., Hochstein, D., Lee, Y. L., Angus, R. D. & Golding, B. (1992) Lipopolysaccharide (LPS) from Brucella abortus is less toxic than that from Escherichia coli, suggesting the possible use of B. abortus or LPS from B. abortus as carrier in vaccines. Infect Immun, 60, 1385–9.
Gorvel, J. -P. (2008) Brucella: a Mr “Hide” converted into Dr Jekyll. Microbes Infect, 10, 1010–13.
Hernandez-Mora, G., Gonzales-Barrientos, R., Morales, J. A., Chaves-Olarte, E., Guzman-Verri, C., Baqueiro-Calvo, E., De-Miguel, M. J., Marin, C. M., Blasco, J. M., & Moreno, E. (2008) Neurobrucellosis in stranded dolphins, Costa Rica. Emerg Infect Dis, 14, 1430–3.
Herzberg, M. & Elberg, S. (1953) Immunization against Brucella infection 1. Isolation and characterization of a streptomycin-dependent mutant. J Bacteriol, 66, 585–99.
Herzberg, M. & 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, 432–5.
Herzberg, M., Elberg, S. S. & Meyer, K. F. (1953) Immunization against Brucella infection. II. Effectiveness of a streptomycin-dependent strain of Brucella. J Bacteriol, 66, 600–5.
Kumar, Y. & Valdivia, R. H. (2009) Leading a sheltered life: intracellular pathogens and maintenance of vacuolar compartments. Cell Host Microbe, 5, 593–1001.
Lang, R., Banai, M., Lishner, M. & Rubinstein, E. (1995) Brucellosis. Intl J Antimicrob Agents, 5, 203–8.
Letesson, J. J., Tibor, A., Van Yynde, G., Wansard, V., Weynants, V., Denoel, P. & Saman, E. (1997) Humoral immune responses of Brucella-infected cattle, sheep, and goats to eight purified recombinant Brucella proteins in an indirect enzyme-linked immunosorbent assay. Clin Diagn Lab Immun, 4, 556–64.
Madkour, M. M. (1989) Brucellosis. Butterworths, London, 294.
Meador, V. P. & Deyoe, B. L. (1989) Intracellular localization of Brucella abortus in bovine placenta. Vet Pathol, 26, 513–15.
Neta, A. V. C., Stynen, A. P. R., Paixäo, T. A., Miranda, K. L., Silva, F. L., Rouz, C. M., Tsolis, R. M., Everts, R. E., Lewin, H. A., Carvalho, A. F., Lage, A. P. & Santo, R. L. (2008) Modulation of the bovine trophoblastic innate immune response by Brucella abortus. Infect Immun, 76, 1897–907.
Nicoletti, P. (1980) The epidemiology of bovine brucellosis. Adv Vet Sci Comp Med, 24, 69–98.
Nielsen, K. & Ewalt, D. R. (2008) Bovine brucellosis. Manual of diagnostic tests and vaccines for terrestrial animals, 6th ed. Vol. 2, The Office International des Epizooties, Paris, pp. 624–59,
Nielsen, K., Smith, P., Yu, W., Nicoletti, P., Elzer, P., Robles, C., Bermudez, R., Renteria, T., Moreno, F., Ruiz, A., Massengill, C., Muenks, Q., Jurgersen, G., Tollersrud, T., Samartino, L., Conde, S., Forbes, L., Gall, D., Perez, B., Rojas, X. & Minas, A. (2005) Towards single screening tests for brucellosis. Rev Sci Tec (The Office International des Epizooties, Paris) 24, 1027–38.
Pappas, G., Akritidis, N., Bosilkovski, M. & Tsianos, E. (2005) Brucellosis. New Eng J Med, 352, 2325–36.
Pei, J., Turse, J. E. & Ficht, T. A. (2008) Evidence of Brucella abortus OPS dictating uptake and restricting NF-κB activation in murine macrophages. Microbes Infect, 10, 582–90.
Pizarro-Cerdá, J., Méresse, S., Parton, R. G., Van Der Goot, G., Sola-Landa, A., Lopez-Goñi, I., Moreno, E. & Gorvel, J. -P. (1998) Brucella abortus transits through the autophagic pathway and replicates in the endoplasmic reticulum of nonprofessional phagocytes. Infect Immun, 66, 5711–24.
Rajashekara, G., Glasner, J. D., Glover, D. A. & Splitter, G. A. (2004) Comparative whole-genome hybridization reveals genomic islands in Brucella species. J Bacteriol, 186, 5040–51.
Rambow-Larsen, A. A., Peterson, E. M., Gourley, C. R. & Splitter, G. A. (2009) Brucella regulators: self-control in a hostile environment. Trends Microbiol, 17, 371–77.
Roop II R. M., Gains, J. M., Anderson, E. S., Caswell, C. C. & Martin, D. W. (2009) Survival of the fittest: how Brucella strains adapt to their intracellular niche in the host. Med Microbiol Immun, 198, 221–38.
Saegerman, C., De Waele, L., Gilson, D., Godfroid, J., Thiange, P., Michel, P., Limbourg, B., Vo T. K. -O., Limet, J., Letesson, J. -J. & Berkvens, D. (2004) Evaluation of three serum i-ELISAs using monoclonal antibodies and protein G as peroxidase conjugate for the diagnosis of bovine brucellosis. Vet Microbiol, 100, 91–105.
Samartino, L. E. & Enright, F. M. (1993) Pathogenesis of abortion of bovine brucellosis. Comp Immunol Microbio. Infect Dis, 16, 95–101.
Scholz, H. C., Hubalek, Z., Sedláček, I., Vergnaud, G., Tomaso, H., Dahouk, S., Melzer, F., Kämpfer, P., Neubauer, H., Cloeckaert, A., Maquart, M., Zygmunt, M. S., Whatmore, A. M., Falsen, E., Bahn, P., Göllner, C., Pfeffer, M., Huber, B., Busse, H. -J. & Nöckler, K. (2008) Brucella microti sp. nov., isolated from the common vole Microtus arvalis. Intl J Sys Evol Microbiol, 58, 375–82.
Seleem, M. N., Boyle, S. M. & Sriranganathan, N. (2008) Brucella: a pathogen without classic virulence genes. Vet Microbiol, 129, 1–14.
Smith, H., Williams, A. E., Pearce, J. H., Keppie, J., Harris-Smith, P. W., Fitz-George, R. B. & Witt, K. (1965) Foetal erythritol: a cause of the localization of Brucella abortus in bovine contagious abortion. Nature, 193, 47–9.
Sperry, J. F. & Robertson, D. C. (1975) Erythritol catabolism by Brucella abortus. J Bacteriol, 121, 619–30.
Stevens, M. G., Hennager, S. G., Olsen, S. C. & Cheville, N. F. (1994) Serologic responses in diagnostic tests for brucellosis in cattle vaccinated with Brucella abortus 19 or RB51. J Clin Microbiol, 32, 1065–6.
Swartz, T. E., Tseng, T. -S., Frederickson, M. A., Paris, G., Comerci, D. J., Rajashekara, G., Kim, J. -G., Mudgett, M. B., Splitter, G. A.., Ugalde, R. A., Goldbaum, F. A., Briggs, W. R. & Bogomolni, R. A. (2007) Blue-light-activated histidine kinases: two-component sensors in bacteria. Science, 317, 1090–93.
Tsolis, R. M., Young, G. M., Solnic, J. V. & Bäumler, A. J. (2008) From bench to bedside: stealth of enteroinvasive pathogens. Nat Rev, 6, 883–92.
Wattam, A. R., Williams, K. P., Snyder, E. E., Almeida, N. F. Jr., Shukla, M., Dickerman, A. W., Crasta, O. R., Kenyon, R., Lu, J., Shallom, J. M., Yoo, H., Ficht, T. A., Tsolis, R. M., Munk, C., Tapia, R., Han, C. S., Detter, J. C., Bruce, D., Brettin, T. S., Sobral, B. W., Boyle, S. M. & Setubal, J. C. (2009) Analysis of ten Brucella genomes reveals evidence for horizontal gene transfer despite a preferred intracellular lifestyle. JBacteriol, 191, 3569–79.
Whatmore, A. M. (2009) Current understanding of the genetic diversity of Brucella, an expanding genus of zoonotic pathogens. Infect Genet Evol (doi: 10.1016/j.meegid. 2009.07.001).
Whatmore, A. M., Perrett, L. L. & Mackmillan, A. P. (2007) Characterization of the genetic diversity of Brucella by multilocus sequencing. BMC Microbiol, 7, 34.
Wright, A. E. & Smith, F. (1897) On the application of the serum test to the differential diagnosis of typhoid and Malta fever. Lancet, 1, 656.
Acknowledgements
We are indebted to Klaus Nielsen and his team for conducting i-ELISA, c-ELISA and FPA on the serum samples. Work in the author’s laboratory was partly supported by Binational Agricultural Research and Development Grant US-3829-06 R.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2010 Springer Science+Business Media B.V.
About this paper
Cite this paper
Bardenstein, S., Banai, M. (2010). Brucella Species Synchronize Their Life Cycle to the Gestation Cycle of Their Ruminant Hosts. In: Shafferman, A., Ordentlich, A., Velan, B. (eds) The Challenge of Highly Pathogenic Microorganisms. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-9054-6_14
Download citation
DOI: https://doi.org/10.1007/978-90-481-9054-6_14
Published:
Publisher Name: Springer, Dordrecht
Print ISBN: 978-90-481-9053-9
Online ISBN: 978-90-481-9054-6
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)