Exit Mechanisms of the Intracellular Bacterium Ehrlichia

BACKGROUND: The obligately intracellular bacterium Ehrlichia chaffeensis that resides in mononuclear phagocytes is the causative agent of human monocytotropic ehrlichiosis. Ehrlichia muris and Ixodes ovatus Ehrlichia (IOE) are agents of mouse models of ehrlichiosis. The mechanism by which Ehrlichia are transported from an infected host cell to a non-infected cell has not been demonstrated. METHODOLOGY/PRINCIPAL FINDINGS: Using fluorescence microscopy and transmission and scanning electron microscopy, we demonstrated that Ehrlichia was transported through the filopodia of macrophages during early stages of infection. If host cells were not present in the vicinity of an Ehrlichia-infected cell, the leading edge of the filopodium formed a fan-shaped structure filled with the pathogen. Formation of filopodia in the host macrophages was inhibited by cytochalasin D and ehrlichial transport were prevented due to the absence of filopodia formation. At late stages of infection the host cell membrane was ruptured, and the bacteria were released. CONCLUSIONS/SIGNIFICANCE: Ehrlichia are transported through the host cell filopodium during initial stages of infection, but are released by host cell membrane rupture during later stages of infection.