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

被引：50

作者：

Tsukamoto, Kentaro ^{[1
]}

Shinzawa, Naoaki ^{[2
,9
]}

Kawai, Akito ^{[1
]}

Suzuki, Masahiro ^{[1
]}

Kidoya, Hiroyasu ^{[3
]}

Takakura, Nobuyuki ^{[3
]}

Yamaguchi, Hisateru ^{[4
,10
]}

Kameyama, Toshiki ^{[5
,11
]}

Inagaki, Hidehito ^{[6
,7
]}

Kurahashi, Hiroki ^{[6
,7
]}

Horiguchi, Yasuhiko ^{[5
]}

Doi, Yohei ^{[1
,8
]}

机构：

[1] Fujita Hlth Univ, Dept Microbiol, Sch Med, Toyoake, Aichi 4701192, Japan

[2] Osaka Univ, Res Inst Microbial Dis, Dept Mol Bacteriol, Suita, Osaka 5650871, Japan

[3] Osaka Univ, Res Inst Microbial Dis, Dept Signal Transduct, Suita, Osaka 5650871, Japan

[4] Fujita Hlth Univ, Inst Comprehens Med Sci, Div Biomed Polymer Sci, Toyoake, Aichi 4701192, Japan

[5] Fujita Hlth Univ, Inst Comprehens Med Sci, Div Gene Express Mech, Toyoake, Aichi 4701192, Japan

[6] Fujita Hlth Univ, Inst Comprehens Med Sci, Div Mol Genet, Toyoake, Aichi 4701192, Japan

[7] Fujita Hlth Univ, Genome & Transcriptome Anal Ctr, Toyoake, Aichi 4701192, Japan

[8] Univ Pittsburgh, Div Infect Dis, Sch Med, Pittsburgh, PA 15261 USA

[9] Tokyo Med & Dent Univ, Grad Sch Med & Dent Sci, Dept Environm Parasitol, Bunkyo Ku, Tokyo 1138510, Japan

[10] Yokkaichi Nursing & Med Care Univ, Sch Nursing & Med Care, Dept Med Technol, Yokaichi, Mie 5128045, Japan

[11] Fujita Hlth Univ, Dept Physiol, Sch Med, Toyoake, Aichi 4701192, Japan

来源：

NATURE COMMUNICATIONS | 2020年 / 11卷 / 01期

关键词：

ENDOTHELIAL GROWTH-FACTOR; BACILLARY ANGIOMATOSIS; CELL PROLIFERATION; ESCHERICHIA-COLI; HENSELAE; SECRETION; RECEPTOR; ADHESIN; SYSTEM; INFECTIONS;

D O I：

10.1038/s41467-020-17391-2

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：14

共 65 条

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