The Bartonella autotransporter BafA activates the host VEGF pathway to drive angiogenesis

Abstract

Pathogenic bacteria of the genus Bartonella can induce vasoproliferative lesions during infection. The underlying mechanisms are unclear, but involve secretion of an unidentified mitogenic factor. Here, we use functional transposon-mutant screening in Bartonella henselae to identify such factor as a pro-angiogenic autotransporter, called BafA. The passenger domain of BafA induces cell proliferation, tube formation and sprouting of microvessels, and drives angiogenesis in mice. BafA interacts with vascular endothelial growth factor (VEGF) receptor-2 and activates the downstream signaling pathway, suggesting that BafA functions as a VEGF analog. A BafA homolog from a related pathogen, Bartonella quintana, is also functional. Our work unveils the mechanistic basis of vasoproliferative lesions observed in bartonellosis, and we propose BafA as a key pathogenic factor contributing to bacterial spread and host adaptation.

Schizophrenia and Bartonella spp. Infection: A Pilot Case–Control Study

“…Bartonella spp. can also induce encephalitis and microvascular injury, or could precipitate an autoimmune process, any of which could contribute to pathogenesis of neuropsychiatric symptoms (Scheidegger et al 2011, Fan and Ali 2020, Tsukamoto et al 2020).…”

Melanin Produced by Bordetella parapertussis Confers a Survival Advantage to the Bacterium during Host Infection

“…For generation of the plasmid pMariG used for delivery of the mariner transposon containing the gentamicin resistance (Gm r ) gene, a DNA fragment of ∼0.6 kbp of the Gm r gene was amplified by PCR using pABB-CRS2-Gm as the template with primers pABB-Gm-S and pABB-Gm-AS. Inverse PCR was also performed using pMariK ( 35 ) as the template with primers pMariK-S and pMariK-AS. These PCR products were then ligated using an In-Fusion HD cloning kit.…”

“…Determination of the transposon insertion site was performed as described previously with slight modifications ( 35 ). Briefly, gDNA was extracted from the transposon-integrated mutant using a DNeasy blood and tissue kit (Qiagen) and digested with Sau3AI.…”

Advances in hydrogel-based vascularized tissues for tissue repair and drug screening

“… GFs Main function Ref. VEGF The key regulator of angiogenesis during embryogenesis; promoting ECs migration, proliferation, vascular permeability, and degeneration of ECM through binding to the receptors with tyrosine kinase activity [ 200 , 201 ] bFGF Inducing plasminogen activator and collagenase activity; a strong synergistic action with VEGF accelerating ECs migration [ 202 ] PDGF-B Stabilizing and enclosing the channels of ECs, leading to the maturation of blood vessels [ 203 ] ANG-1 Maintaining the interaction between ECs and surrounding supporting cells and the stability of blood vessel structure [ 184 ] Abbreviations: ANG-1 - angiopoietin-1, bFGF - basic fibroblast growth factors, GFs - growth factors, PDGF-B - platelet-derived GF-B, VEGF - vascular endothelial growth factors. …”