The autotransporter BafA contributes to the pro-angiogenic potential of Bartonella elizabethae.

Bartonella elizabethae is a rat-borne zoonotic bacterium that causes human infectious endocarditis or neuroretinitis. Recently, a case of bacillary angiomatosis (BA) resulting from this organism was reported, leading to speculation that B. elizabethae may also trigger vasoproliferation. However, there are no reports of B. elizabethae promoting human vascular endothelial cell (EC) proliferation or angiogenesis, and to date, the effects of this bacterium on ECs are unknown. We have previously identified BafA, a pro-angiogenic autotransporter secreted from B. henselae and B. quintana, which are recognized as Bartonella spp. responsible for BA in humans. Here, we hypothesized that B. elizabethae also harbored a functional bafA gene and examined the pro-angiogenic activity of recombinant B. elizabethae-derived BafA. The bafA gene of B. elizabethae, which was found to share a 51.1% amino acid identity with BafA of B. henselae and 52.5% with that of B. quintana in the passenger domain, was located in a syntenic region of the genome. The recombinant protein of the N-terminal passenger domain of B. elizabethae-BafA facilitated EC proliferation and capillary structure formation. Furthermore, it also upregulated the receptor signaling pathway of vascular endothelial cell growth factor, as observed in B. henselae-BafA. Taken together, B. elizabethae-derived BafA stimulates human EC proliferation and may contribute to the pro-angiogenic potential of this bacterium. So far, functional bafA genes have been found in all BA-causing Bartonella spp., supporting the key role BafA may play in BA pathogenesis. This article is protected by copyright. All rights reserved.