Bartonella quintana causes trench fever, endocarditis, and the vasculoproliferative disorders bacillary angiomatosis and peliosis hepatis in humans. Little is known about the interaction of this pathogen with host cells. We attempted to elucidate the interaction of B. quintana with human macrophages (THP-1) and epithelial cells (HeLa 229). Remarkably, only B. quintana strain JK-31 induced secretion of vascular endothelial growth factor (VEGF) from THP-1 and HeLa 229 cells upon infection similar to the secretion induced by B. henselae Marseille, whereas other strains (B. quintana 2-D70, B. quintana Toulouse, and B. quintana Munich) did not induce such secretion. Immunofluorescence testing and electron microscopy revealed that the B. quintana strains unable to induce VEGF secretion did not express the variable outer membrane proteins (Vomps) on their surfaces. Surprisingly, the increase in VEGF secretion mediated by B. quintana JK-31 was not paralleled by elevated host cell adherence rates compared with the rates for Vomp-negative B. quintana strains. Our results suggest that the Vomps play a leading role in the angiogenic reprogramming of host cells by B. quintana but not in the adherence to host cells.Bartonella quintana and Bartonella henselae are reemerging, gram-negative, facultative intracellular bacteria which cause a variety of human diseases. B. henselae is the most common cause of cat scratch disease. In immunocompromised patients (e.g., AIDS patients), both B. henselae and the closely related species B. quintana (1) cause the vasculoproliferative disorders bacillary angiomatosis (BA) and peliosis hepatis (PH) (20). Infections with B. quintana can result in "trench fever," which is characterized by periodic feverish relapses every fifth day due to intraerythrocytic bacteremia (12). B. quintana was most important during World War I, when more than one million soldiers suffered from this disease. The confirmed transmission vector is the human body louse (33). Today, B. quintana is a well-recognized cause of fever, bacteremia, and endocarditis in human immunodeficiency virus-seronegative, inner-city patients living under poor hygienic conditions, such as the homeless or alcoholics (5, 13, 43). Prolonged periods of intracellular erythrocyte parasitism appear to be a crucial aspect of the pathogenicity of Bartonella spp. (21, 38).Very little is known about the pathogenicity of B. quintana. It has been shown that Bartonella spp. replicate within endothelial cells in a Bartonella-containing vacuole (6), adhere to endothelial and epithelial cells (3, 9, 17), and invade erythrocytes (36, 39). There is also evidence that B. quintana might interact with human erythroblast cells (37). Contradictory results about the induction of apoptosis by B. quintana have been obtained; while early during B. quintana infection apoptosis of endothelial cells was detectable, this apoptosis was inhibited at later times (26). Recently, variably expressed outer membrane proteins VompA, VompB, VompC, and VompD mediating collagen bindin...