Cyclic β-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 (CbG) synthesized by brucella is important for circumventing host cell defenses. CbG acted in lipid rafts found on host cell membranes. CbG-deficient mutants failed to prevent phagosome-lysosome fusion and could not replicate. However, when treated with purified CbG 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 CbG. Brucella CbG is thus a virulence factor that interacts with lipid rafts and contributes to pathogen survival.