Chapter 27 : , a Perfect Trojan Horse in Phagocytes

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Several species of the genus are responsible for brucellosis: , , , , , and . has also been isolated from a variety of terrestrial wildlife mammal species such as elk, buffalo, reindeer, and bison as well as from marine mammals, illustrating its broad host range. Currently, of the six main species of , four can cause disease in humans, with having the most severe pathogenicity, followed by , which is more rare but still presents severe pathogenicity, and then and , which are less pathogenic in humans. Significant progress has been made in our understanding of the virulence factors that enable to reside within phagocytic cells and escape their killing mechanisms. In essence, is able to proliferate extensively within both macrophages and nonphagocytic epithelial cells without affecting their basic cellular functions or inducing cell death. It efficiently controls its own intracellular trafficking in order to avoid degradation within lysosomes and reach an intracellular compartment suited for replication, which we commonly designate as the -containing vacuole (BCV). Several virulence factors have been implicated in Brucella resistance to cellular defensive mechanisms and interaction with cellular pathways to create the environment suited for its intracellular survival. In recent years great advances have been made in our understanding of its pathogenesis, due in particular to the availability of the genome sequences.

Citation: Salcedo S, Gorvel J. 2009. , a Perfect Trojan Horse in Phagocytes, p 427-435. In Russell D, Gordon S (ed), Phagocyte-Pathogen Interactions. ASM Press, Washington, DC. doi: 10.1128/9781555816650.ch27
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1. Anderson, T. D.,, and N. F. Cheville. 1986. Ultrastructural morphometric analysis of Brucella abortus-infected tropho-blasts in experimental placentitis. Bacterial replication occurs in rough endoplasmic reticulum. Am. J. Pathol. 124:226237.
2. Arellano-Reynoso, B.,, N. Lapaque,, S. Salcedo,, G. Briones,, A. E. Ciocchini,, R. Ugalde,, E. Moreno,, I. Moriyon, and, J. P. Gorvel. 2005. Cyclic beta-1,2-glucan is a Brucella virulence factor required for intracellular survival. Nat. Immunol. 6:618625.
3. Barquero-Calvo, E.,, E. Chaves-Olarte,, D. S. Weiss,, C. Guzman-Verri,, C. Chacon-Diaz,, A. Rucavado,, I. Moriyon, and, E. Moreno. 2007. Brucella abortus uses a stealthy strategy to avoid activation of the innate immune system during the onset of infection. PLoS ONE 2:e631.
4. Bellaire, B. H.,, R. M. Roop, II, and, J. A. Cardelli. 2005. Opsonized virulent Brucella abortus replicates within non-acidic, endoplasmic reticulum-negative, LAMP-1-positive phagosomes in human monocytes. Infect. Immun. 73:37023713.
5. Berguer, P. M.,, J. Mundinano,, I. Piazzon, and, F. A. Goldbaum. 2006. A polymeric bacterial protein activates dendritic cells via TLR4. J. Immunol. 176:23662372.
6. Billard, E.,, C. Cazevieille,, J. Dornand, and, A. Gross. 2005. High susceptibility of human dendritic cells to invasion by the intracellular pathogens Brucella suis, B. abortus, and B. melitensis. Infect. Immun. 73:84188424.
7. Bohin, J. P. 2000. Osmoregulated periplasmic glucans in Proteobacteria. FEMS Microbiol. Lett. 186:1119.
8. Boschiroli, M. L.,, S. Ouahrani-Bettache,, V. Foulongne,, S. Michaux-Charachon,, G. Bourg,, A. Allardet-Servent,, C. Cazevieille,, J. P. Liautard,, M. Ramuz, and, D. O’Callaghan. 2002. The Brucella suis virB operon is induced intracellularly in macrophages. Proc. Natl. Acad. Sci. USA 99:15441549.
9. Briones, G.,, N. Inon de Iannino,, M. Roset,, A. Vigliocco,, P. S. Paulo, and, R. A. Ugalde. 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. 69:45284535.
10. Celli, J.,, C. de Chastellier,, D. M. Franchini,, J. Pizarro-Cerda,, E. Moreno, and, J. P. Gorvel. 2003. Brucella evades macrophage killing via VirB-dependent sustained interactions with the endoplasmic reticulum. J. Exp. Med. 198:545556.
11. Celli, J.,, S. P. Salcedo, and, J. P. Gorvel. 2005. Brucella coopts the small GTPase Sar1 for intracellular replication. Proc. Natl. Acad. Sci. USA 102:16731678.
12. Chaves-Olarte, E.,, C. Guzman-Verri,, S. Meresse,, M. Desjardins,, J. Pizarro-Cerda,, J. Badilla,, J. P. Gorvel, and, E. Moreno. 2002. Activation of Rho and Rab GTPases dissociates Brucella abortus internalization from intracellular trafficking. Cell. Microbiol. 4:663676.
13. Comerci, D. J.,, S. Altabe,, D. de Mendoza, and, R. A. Ugalde. 2006. Brucella abortus synthesizes phosphatidylcholine from choline provided by the host. J. Bacteriol. 188:19291934.
14. Comerci, D. J.,, M. J. Martinez-Lorenzo,, R. Sieira,, J. P. Gorvel, and, R. A. Ugalde. 2001. Essential role of the VirB machinery in the maturation of the Brucella abortus-containing vacuole. Cell. Microbiol. 3:159168.
15. Conde-Alvarez, R.,, M. J. Grillo,, S. P. Salcedo,, M. J. de Miguel,, E. Fugier,, J. P. Gorvel,, I. Moriyon, and, M. Iriarte. 2006. Synthesis of phosphatidylcholine, a typical eukaryotic phospholipid, is necessary for full virulence of the intracellular bacterial parasite Brucella abortus. Cell. Microbiol. 8:13221335.
16. Delrue, R. M.,, C. Deschamps,, S. Leonard,, C. Nijskens,, I. Danese,, J. M. Schaus,, S. Bonnot,, J. Ferooz,, A. Tibor,, X. De Bolle, and, J. J. Letesson. 2005. A quorum-sensing regulator controls expression of both the type IV secretion system and the flagellar apparatus of Brucella melitensis. Cell. Microbiol. 7:11511161.
17. Delrue, R. M.,, M. Martinez-Lorenzo,, P. Lestrate,, I. Danese,, V. Bielarz,, P. Mertens,, X. De Bolle,, A. Tibor,, J. P. Gorvel, and, J. J. Letesson. 2001. Identification of Brucella spp. genes involved in intracellular trafficking. Cell. Microbiol. 3:487497.
18. Dozot, M.,, R. A. Boigegrain,, R. M. Delrue,, R. Hallez,, S. Ouahrani-Bettache,, I. Danese,, J. J. Letesson,, X. De Bolle, and, S. Kohler. 2006. The stringent response mediator Rsh is required for Brucella melitensis and Brucella suis virulence, and for expression of the type IV secretion system virB. Cell. Microbiol. 8:17911802.
19. Endley, S.,, D. McMurray, and, T. A. Ficht. 2001. Interruption of the cydB locus in Brucella abortus attenuates intracellular survival and virulence in the mouse model of infection. J. Bacteriol. 183:24542462.
20. Eskra, L.,, A. Mathison, and, G. Splitter. 2003. Microarray analysis of mRNA levels from RAW264.7 macrophages infected with Brucella abortus. Infect. Immun. 71:11251133.
21. Fernandes, D. M.,, and C. L. Baldwin. 1995. Interleukin-10 downregulates protective immunity to Brucella abortus. Infect. Immun. 63:11301133.
22. Fontes, P.,, M. T. Alvarez-Martinez,, A. Gross,, C. Carnaud,, S. Kohler, and, J. P. Liautard. 2005. Absence of evidence for the participation of the macrophage cellular prion protein in infection with Brucella suis. Infect. Immun. 73:62296236.
23. Forestier, C.,, F. Deleuil,, N. Lapaque,, E. Moreno, and, J. P. Gorvel. 2000. Brucella abortus lipopolysaccharide in murine peritoneal macrophages acts as a down-regulator of T cell activation. J. Immunol. 165:52025210.
24. Forestier, C.,, E. Moreno,, J. Pizarro-Cerda, and, J. P. Gorvel. 1999. Lysosomal accumulation and recycling of lipopolysaccharide to the cell surface of murine macrophages, an in vitro and in vivo study. J. Immunol. 162:67846791.
25. Foulongne, V.,, G. Bourg,, C. Cazevieille,, S. Michaux-Charachon, and, D. O’Callaghan. 2000. Identification of Brucella suis genes affecting intracellular survival in an in vitro human macrophage infection model by signature-tagged transposon mutagenesis. Infect. Immun. 68:12971303.
26. Fretin, D.,, A. Fauconnier,, S. Kohler,, S. Halling,, S. Leonard,, C. Nijskens,, J. Ferooz,, P. Lestrate,, R. M. Delrue,, I. Danese,, J. Vandenhaute,, A. Tibor,, X. DeBolle, and, J. J. Letesson. 2005. The sheathed flagellum of Brucella melitensis is involved in persistence in a murine model of infection. Cell. Microbiol. 7:687698.
27. Giambartolomei, G. H.,, A. Zwerdling,, J. Cassataro,, L. Bruno,, C. A. Fossati, and, M. T. Philipp. 2004. Lipoproteins, not lipopolysaccharide, are the key mediators of the proinflammatory response elicited by heat-killed Brucella abortus. J. Immunol. 173:46354642.
28. Gross, A.,, A. Terraza,, S. Ouahrani-Bettache,, J. P. Liautard, and, J. Dornand. 2000. In vitro Brucella suis infection prevents the programmed cell death of human monocytic cells. Infect. Immun. 68:342351.
29. He, Y.,, S. Reichow,, S. Ramamoorthy,, X. Ding,, R. Lathigra,, J. C. Craig,, B. W. Sobral,, G. G. Schurig,, N. Srirangana-than, and, S. M. Boyle. 2006. Brucella melitensis triggers time-dependent modulation of apoptosis and down-regulation of mitochondrion-associated gene expression in mouse macrophages. Infect. Immun. 74:50355046.
30. Hong, P. C.,, R. M. Tsolis, and, T. A. Ficht. 2000. Identification of genes required for chronic persistence of Brucella abortus in mice. Infect. Immun. 68:41024107.
31. Inon de Iannino, N.,, G. Briones,, M. Tolmasky, and, R. A. Ugalde. 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. 180:43924400.
32. Iyankan, L.,, and D. K. Singh. 2002. The effect of Brucella abortus on hydrogen peroxide and nitric oxide production by bovine polymorphonuclear cells. Vet. Res. Commun. 26:93102.
33. Jimenez de Bagues, M. P.,, A. Terraza,, A. Gross, and, J. Dornand. 2004. Different responses of macrophages to smooth and rough Brucella spp.: relationship to virulence. Infect. Immun. 72:24292433.
34. Kim, S.,, M. Watarai,, H. Suzuki,, S. Makino,, T. Kodama, and, T. Shirahata. 2004. Lipid raft microdomains mediate class A scavenger receptor-dependent infection of Brucella abortus. Microb. Pathog. 37:1119.
35. Lapaque, N.,, F. Forquet,, C. de Chastellier,, Z. Mishal,, G. Jolly,, E. Moreno,, I. Moriyon,, J. E. Heuser,, H. T. He, and, J. P. Gorvel. 2006a. Characterization of Brucella abortus lipopolysaccharide macrodomains as mega rafts. Cell. Microbiol. 8:197206.
36. Lapaque, N.,, I. Moriyon,, E. Moreno, and, J. P. Gorvel. 2005. Brucella lipopolysaccharide acts as a virulence factor. Curr. Opin. Microbiol. 8:6066.
37. Lapaque, N.,, O. Takeuchi,, F. Corrales,, S. Akira,, I. Moriyon,, J. C. Howard, and, J. P. Gorvel. 2006b. Differential inductions of TNF-alpha and IGTP, IIGP by structurally diverse classic and non-classic lipopolysaccharides. Cell. Microbiol. 8:401413.
38. Lavigne, J. P.,, G. Patey,, F. J. Sangari,, G. Bourg,, M. Ramuz,, D. O’Callaghan, and, S. Michaux-Charachon. 2005. Identification of a new virulence factor, BvfA, in Brucella suis. Infect. Immun. 73:55245529.
39. Martinez de Tejada, G.,, J. Pizarro-Cerda,, E. Moreno, and, I. Moriyon. 1995. The outer membranes of Brucella spp. are resistant to bactericidal cationic peptides. Infect. Immun. 63:30543061.
40. Meador, V. P.,, and B. L. Deyoe. 1989. Intracellular localization of Brucella abortus in bovine placenta. Vet. Pathol. 26:513515.
41. Naroeni, A.,, and F. Porte. 2002. Role of cholesterol and the ganglioside GM(1) in entry and short-term survival of Brucella suis in murine macrophages. Infect. Immun. 70:16401644.
42. O’Callaghan, D.,, C. Cazevieille,, A. Allardet-Servent,, M. L. Boschiroli,, G. Bourg,, V. Foulongne,, P. Frutos,, Y. Kulakov, and, M. Ramuz. 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. 33:12101220.
43. Orduna, A.,, C. Orduna,, J. M. Eiros,, M. A. Bratos,, P. Gutierrez,, P. Alonso, and, A. Rodriguez Torres. 1991. Inhibition of the degranulation and myeloperoxidase activity of human polymorphonuclear neutrophils by Brucella melitensis. Microbiologia 7:113119.
44. Pappas, G.,, P. Papadimitriou,, N. Akritidis,, L. Christou, and, E. V. Tsianos. 2006. The new global map of human brucellosis. Lancet Infect. Dis. 6:9199.
45. Pizarro-Cerda, J.,, S. Meresse,, R. G. Parton,, G. van der Goot,, A. Sola-Landa,, I. Lopez-Goni,, E. Moreno, and, J. P. Gorvel. 1998. Brucella abortus transits through the autophagic pathway and replicates in the endoplasmic reticulum of nonprofessional phagocytes. Infect. Immun. 66:57115724.
46. Porte, F.,, J. P. Liautard, and, S. Kohler. 1999. Early acidification of phagosomes containing Brucella suis is essential for intracellular survival in murine macrophages. Infect. Immun. 67:40414047.
47. Porte, F.,, A. Naroeni,, S. Ouahrani-Bettache, and, J. P. Liautard. 2003. Role of the Brucella suis lipopolysaccharide O antigen in phagosomal genesis and in inhibition of phagosome-lysosome fusion in murine macrophages. Infect. Immun. 71:14811490.
48. Rajashekara, G.,, D. A. Glover,, M. Krepps, and, G. A. Splitter. 2005. Temporal analysis of pathogenic events in virulent and avirulent Brucella melitensis infections. Cell. Microbiol. 7:14591473.
49. Rasool, O.,, E. Freer,, E. Moreno, and, C. Jarstrand. 1992. Effect of Brucella abortus lipopolysaccharide on oxidative metabolism and lysozyme release by human neutrophils. Infect. Immun. 60:16991702.
50. Riley, L. K.,, and D. C. Robertson. 1984a. Brucellacidal activity of human and bovine polymorphonuclear leukocyte granule extracts against smooth and rough strains of Brucella abortus. Infect. Immun. 46:231236.
51. Riley, L. K.,, and D. C. Robertson. 1984b. Ingestion and intracellular survival of Brucella abortus in human and bovine polymorphonuclear leukocytes. Infect. Immun. 46:224230.
52. Rittig, M. G.,, M. T. Alvarez-Martinez,, F. Porte,, J. P. Liautard, and, B. Rouot. 2001. Intracellular survival of Brucella spp. in human monocytes involves conventional uptake but special phagosomes. Infect. Immun. 69:39954006.
53. Robertson, G. T.,, and R. M. Roop, Jr. 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. 34:690700.
54. Rolan, H. G.,, and R. M. Tsolis. 2007. Mice lacking components of adaptive immunity show increased Brucella abortus virB mutant colonization. Infect. Immun. 75:29652973.
55. Sieira, R.,, D. J. Comerci,, D. O. Sanchez, and, R. A. Ugalde. 2000. A homologue of an operon required for DNA transfer in Agrobacterium is required in Brucella abortus for virulence and intracellular multiplication. J. Bacteriol. 182:48494855.
56. Sola-Landa, A.,, J. Pizarro-Cerda,, M. J. Grillo,, E. Moreno,, I. Moriyon,, J. M. Blasco,, J. P. Gorvel, and, I. Lopez-Goni. 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. 29:125138.
57. Spera, J. M.,, J. E. Ugalde,, J. Mucci,, D. J. Comerci, and, R. A. Ugalde. 2006. A B lymphocyte mitogen is a Brucella abortus virulence factor required for persistent infection. Proc. Natl. Acad. Sci. USA 103:1651416519.
58. Watarai, M.,, S. Kim,, J. Erdenebaatar,, S. Makino,, M. Horiuchi,, T. Shirahata,, S. Sakaguchi, and, S. Katamine. 2003. Cellular prion protein promotes Brucella infection into macrophages. J. Exp. Med. 198:517.
59. Watarai, M.,, S. Makino,, Y. Fujii,, K. Okamoto, and, T. Shirahata. 2002. Modulation of Brucella-induced macropinocytosis by lipid rafts mediates intracellular replication. Cell. Microbiol. 4:341355.
60. Weiss, D. S.,, K. Takeda,, S. Akira,, A. Zychlinsky, and, E. Moreno. 2005. MyD88, but not toll-like receptors 4 and 2, is required for efficient clearance of Brucella abortus. Infect. Immun. 73:51375143.

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