Intracellular survival of Brucella: defining the link with persistence.

Brucellosis is caused by a facultative intracellular pathogen that invades both professional and non-professional phagocytic cells. Resistance to killing in professional phagocytic cells controls survival and chronic infection. Resistance of the organism to killing appears to derive from altered intracellular trafficking of Brucella containing vacuoles to the endoplasmic reticulum via the autophagic pathway. Acute infection is observed in pregnant ruminants in which invasion of the chorionic trophoblasts results in abortion. Following abortion persistence of the organism is observed in the mammary gland and lymph nodes of ruminants. The risk of multiple abortions and subsequent shedding of the organism in the milk has resulted in the culling of infected animals. Persistence of the organism in the reticuloendothelial system is a primary symptom in human infection and may persist over several decades. We have employed the mouse model of brucellosis to characterize genes responsible for persistent infection in an effort to identify potential drug targets for elimination of infection or to attenuate potential vaccine candidates. The results suggest that Brucella utilizes a battery of metabolic functions to sustain itself in intracellular environments in conjunction with altering the intracellular course of infection.