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

Kentaro Tsukamoto, Naoaki Shinzawa, Akito Kawai, Masahiro Suzuki, Hiroyasu Kidoya, Nobuyuki Takakura, Hisateru Yamaguchi, Toshiki Kameyama, Hidehito Inagaki, Hiroki Kurahashi, Yasuhiko Horiguchi, Yohei Doi

Research output: Contribution to journalArticle

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.

Original languageEnglish
Article number3571
JournalNature communications
Volume11
Issue number1
DOIs
Publication statusPublished - 01-12-2020

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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