TY - JOUR
T1 - The Bartonella autotransporter BafA activates the host VEGF pathway to drive angiogenesis
AU - Tsukamoto, Kentaro
AU - Shinzawa, Naoaki
AU - Kawai, Akito
AU - Suzuki, Masahiro
AU - Kidoya, Hiroyasu
AU - Takakura, Nobuyuki
AU - Yamaguchi, Hisateru
AU - Kameyama, Toshiki
AU - Inagaki, Hidehito
AU - Kurahashi, Hiroki
AU - Horiguchi, Yasuhiko
AU - Doi, Yohei
N1 - Funding Information:
We thank Akio Abe and Asaomi Kuwae for providing pCVD442 and pCACTUS-Tp, Hiroki Nagai for pNH3503. We thank Suzu Katade for assistance with transposon-mutant screening, and Takao Tsuji, Yusuke Minato, and Keisuke Hitachi for their helpful comments. The imaging analysis using Opera Phenix HCS and the nano-LS–MS/MS analysis using Orbitrap Fusion ETD MS were performed at the Center for Joint Research Facilities Support of Fujita Health University. This work was supported by JSPS KAKENHI Grant Number JP19K07548 (K.T.), MEXT-Supported Program for the Strategic Research Foundation at Private Universities from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (H. Kurahashi), and the Grant for Joint Research Project of the Research Institute for Microbial Diseases, Osaka University (K.T.).
Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12/1
Y1 - 2020/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85087986772&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85087986772&partnerID=8YFLogxK
U2 - 10.1038/s41467-020-17391-2
DO - 10.1038/s41467-020-17391-2
M3 - Article
C2 - 32678094
AN - SCOPUS:85087986772
SN - 2041-1723
VL - 11
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 3571
ER -