[S4-2] Bartonella autotransporter BafA: A novel virulence factor for a bacterial survival strategy
The α-proteobacterial genus Bartonella are hemotropic, facultative intracellular Gram-negative bacteria that lead to infection in mammals including humans. B. henselae, which is the most well-studied species in bartonellae, can cause cat-scratch disease and bacillary angiomatosis. During infection, the bacteria induce vasoproliferative lesions with abnormal endothelial cell proliferation. Vascular endothelial cells appear to be a suitable growth environment for Bartonella to escape from host immune systems, and they target those cells as a strategy for host adaptation. The formation of such vasoproliferative lesions has been regarded as a hallmark of Bartonella infection not found in other pathogenic bacteria. However, the underlying mechanisms how the organisms increase endothelial cells are fully unclear, but involve secretion of an unidentified mitogenic factor. Recently, we successfully identified such factor as a pro-angiogenic autotransporter, named BafA (Tsukamoto K. et al., Nat Commun, 2020). BafA interacts with vascular endothelial growth factor (VEGF) receptor-2 and activates the downstream signaling pathway, suggesting that BafA functions as a VEGF analogue. Our study reveals the mechanistic basis of the formation of vasoproliferative lesions in bartonellosis, and we propose BafA as a key virulence factor contributing to bacterial survival and host adaptation.