Scientists from Fujita Health University (Aichi, Japan) have discovered a pro-angiogenic autotransporter released by bacteria of the genus Bartonella, which they have named Bartonella angiogenic factor A (BafA). This is the very first report of a vascular endothelial growth factor (VEGF)-like protein produced by bacteria, and gives insight into how these bacteria give rise to lesions in the human body. The findings are available to read in Nature Communications.
Upon introducing Bartonella henselae (B. henselae) into human endothelial cells in vitro, the researchers observed that these bacteria caused the endothelial cells to proliferate. They then induced random mutations in the DNA of the bacteria to identify the genes that give B. henselae the ability to stimulate angiogenesis. This led them to discover that B. henselae can only stimulate angiogenesis in endothelial cells if it has a functional copy of BafA.
The team then extracted samples of the aorta from mice and placed them into gels with or without BafA. The aorta samples that were exposed to BafA grew new blood vessels, whereas the aorta samples not exposed to BafA did not grow new blood vessels.
Further in vitro experiments with human endothelial cells demonstrated that BafA activates cell surface receptors that recognize VEGF. When BafA bound to these receptors, it triggered the activation of MAPK and ERK proteins. These pathways also have important roles in angiogenesis.
“In the last set of experiments, we performed similar studies in a related bacterium called Bartonella quintana, the bacterium that causes trench fever, and we found that it produces its own version of BafA that also causes human endothelial cells to multiply,” commented Kentaro Tsukamoto (Fujita Health University).
The results further the understanding of the mechanisms by which bacteria produce lesions in their hosts.
“We believe that BafA proteins can be leveraged as tools for studying angiogenesis, and we also consider potential medical benefits,” explained Yohei Doi. “Most importantly, BafA is a potential target for the development of diagnostic and therapeutic strategies for bartonellosis.”
The research team hope that one day BafA proteins could be used in regenerative medicine.
Sources: Tsukamoto K, Shinzawa N, Kawai N, et al. The Bartonella autotransporter BafA activates the host VEGF pathway to drive angiogenesis. Nat. Commun. 11 (3571) (2020); www.fujita-hu.ac.jp/en/news/kka9ar0000000gjj.html