The Bartonella autotransporter BafA activates the host VEGF pathway to drive angiogenesis
The Bartonella autotransporter BafA activates the host VEGF pathway to drive angiogenesis
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巴尔通体自转运蛋白 BafA 激活宿主 VEGF 途径以驱动血管生成
DOI：
10.1038/s41467-020-17391-2
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发表时间：
2020
影响因子：
16.6
通讯作者：
Doi Yohei
中科院分区：
文献类型：
--
作者：
Tsukamoto Kentaro;Shinzawa Naoaki;Kawai Akito;Suzuki Masahiro;Kidoya Hiroyasu;Takakura Nobuyuki;Yamaguchi Hisateru;Kameyama Toshiki;Inagaki Hidehito;Kurahashi Hiroki;Horiguchi Yasuhiko;Doi Yohei
巴尔通体菌属致病菌在感染过程中诱导血管增生性病变。潜在的机制尚不清楚，但涉及分泌一种未知的有丝分裂因子。在这里，我们在亨塞巴尔通体中使用功能性转座子突变筛选来确定这种因子是一种促血管生成的自转运蛋白，称为BafA。BafA的乘客域诱导细胞增殖、微血管形成和发芽，并促进小鼠血管生成。BafA与血管内皮生长因子（VEGF）受体-2相互作用并激活下游信号通路，表明BafA具有VEGF类似物的功能。来自相关病原体金塔纳巴尔通体的BafA同源物也具有功能。我们的工作揭示了巴尔通体病血管增生性病变的机制基础，我们提出BafA是促进细菌传播和宿主适应的关键致病因素。
Pathogenic bacteria of the genusBartonellacan 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 inBartonella henselaeto 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.