Cyclic beta-1,2-glucan is a Brucella virulence factor required for intracellular survival.
Pathogenic brucella bacteria have developed strategies to persist for prolonged periods of time in host cells, avoiding innate immune responses. Here we show that the cyclic beta-1,2-glucans (CbetaG) synthesized by brucella is important for circumventing host cell defenses. CbetaG acted in lipid rafts found on host cell membranes. CbetaG-deficient mutants failed to prevent phagosome-lysosome fusion and could not replicate. However, when treated with purified CbetaG or synthetic methyl-beta-cyclodextrin, the mutants were able to control vacuole maturation by avoiding lysosome fusion, and this allowed intracellular brucella to survive and reach the endoplasmic reticulum. Fusion between the endoplasmic reticulum and the brucella-containing vacuole depended on the brucella virulence type IV secretion system but not on CbetaG. Brucella CbetaG is thus a virulence factor that interacts with lipid rafts and contributes to pathogen survival.
Arellano-Reynoso
Beatriz
B
Centre d'Immunologie, Institut National de la Santé et de la Recherche Médicale-Centre National de la Recherche Scientifique de Marseille-Luminy, Case 906, 13288 Marseille CEDEX 9, France.
Lapaque
Nicolas
N
Salcedo
Susana
S
Briones
Gabriel
G
Ciocchini
Andrés Eduardo
AE
Ugalde
Rodolfo
R
Moreno
Edgardo
E
Moriyón
Ignacio
I
Gorvel
Jean-Pierre
JP
D000818:Animals; D002003:Brucella abortus / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity*; D004721:Endoplasmic Reticulum / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D005798:Genes, Bacterial; D006367:HeLa Cells; D006801:Humans; D007113:Immunity, Innate; D066298:In Vitro Techniques; D008247:Lysosomes / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D008561:Membrane Fusion; D021962:Membrane Microdomains / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D010588:Phagosomes / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D014617:Vacuoles / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D014774:Virulence; D047071:beta-Glucans / Q000276:immunology / Q000378:metabolism*
D047071:beta-Glucans; C080135:cyclic beta(1-2)glucan