Author: Fujita Health University, Japan (i): Contact: fujita-hu.ac.jp/en/index.html
Published: 2020-07-22
Table of contents and important points:
The study provides insights into the BafA protein, which can be further used in regenerative medicine to replace or regenerate lost or damaged body parts.
These results provide valuable insights into the mechanisms by which infectious bacteria can create lesions in their hosts.
Further experiments with human endothelial cells in Petri dishes showed that BafA activated cell surface receptors that recognize VEGF.
Main digestion
The study, published in Nature Communications, provides insight into a protein called BafA, which stimulates the production of new blood vessels that support bacterial lesions. This discovery can help develop new methods of diagnosing and treating bartonellosis, and BafA can continue to be used in regenerative medicine to replace or regenerate lost or damaged body parts.
Lesion of fate
How a parasitic bacterium induces the formation of blood vessels to cause lesions
Scientists gain insights into how pathogenic bacteria of the genus Bartonella lead to lesions in the human body and open up new avenues in modern medicine
A team of researchers from Fujita Health University, Japan, found that bacteria of the genus Bartonella release a protein they call BafA that stimulates the production of new blood vessels that support bacterial lesions. This discovery could help scientists develop new ways to diagnose and treat these infections.
Bacteria of the genus Bartonella are parasites that can be transmitted to humans via insect bites and animal scratches and lead to an infection known as “bartonellosis”.
Cat scratch disease and trench fever are forms of bartonellosis caused by different species of Bartonella that infect humans. Bartonella bacteria can cause lesions to appear in the skin and internal organs. To provide a safe habitat, the bacteria increase the number of “vascular endothelial cells” (cells that line the inside of blood vessels) that hide from the host’s immune system and stimulate the formation of new blood vessels through a process called “angiogenesis” .
Previous studies on Bartonella henselae (B. henselae for short), the bacterium responsible for cat scratch disease, have shown that it can “inject” proteins that inhibit programmed cell death (apoptosis) directly into the endothelial cells. However, B. henselae can also promote angiogenesis without directly contacting endothelial cells, which implies that the bacterium can secrete a bioactive substance that does the job of stimulating angiogenesis.
In a new study published in Nature Communications, a team of scientists led by Senior Assistant Professor Kentaro Tsukamoto and Professor Yohei Doi of Fujita Health University, Japan, found that this bioactive substance is actually a protein. They also called this protein Bartonella angiogenic factor A or “BafA” for short. This is the very first report of a vascular endothelial growth factor (VEGF for short) -like protein produced by bacteria.
Figure 1. This study identifies the molecular mechanism by which Bartonella bacteria cause lesions to appear over a patient’s body. Photo courtesy of Kentaro Tsukamoto
The scientists began their project by introducing B. henselae into human endothelial cells in Petri dishes and observed that the bacteria caused the endothelial cells to multiply.
To identify the genes that give B. henselae this ability, the researchers began to induce random mutations in the DNA of the bacteria and to test whether the mutated bacteria could still multiply the endothelial cells.
Through these experiments, the scientists found that B. henselae can only stimulate angiogenesis in human endothelial cells if it has a functional copy of the gene that “codes” for the BafA protein or controls its synthesis. They also observed that exposure of human cells to the isolated BafA protein caused the cells to multiply.
To confirm that BafA stimulates angiogenesis, the scientists extracted samples of a main blood vessel called the aorta from mice and placed the samples in gels that contained BafA or not. As can be seen in the image below, the aortic samples that were not exposed to BafA did not sprout new blood vessels, but the aortic samples that were exposed to BafA grew vessels that extended into the gel. The scientists also found that surgical placement of a BafA-containing gel plug in living mice caused blood vessels from surrounding tissue to grow into the gel.
Figure 2. Aortic tissues that were not exposed to BafA (left) did not sprout from new vessels, while BafA-exposed aortic tissues (right) did. Photo courtesy of Kentaro Tsukamoto
Further experiments with human endothelial cells in Petri dishes showed that BafA activated cell surface receptors that recognize VEGF.
By binding to these receptors, BafA triggered a process within cells that involved proteins called mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinases (ERKs). The MAPK / ERK pathway plays an important role in endothelial cell proliferation and angiogenesis.
“In the last series of experiments, we did similar studies on 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,” explains Dr. Tsukamoto.
These results provide valuable insights into the mechanisms by which infectious bacteria can create lesions in their hosts. “We believe that BafA proteins can be used as tools to study angiogenesis, and we are also considering potential medical benefits,” reports Prof. Doi. “Above all,” he explains, “BafA is a potential target for developing diagnostic and therapeutic strategies for bartonellosis.”
The scientists also speculate that BafA proteins could be used in regenerative medicine, a highly specialized branch of medicine that deals with replacing or regenerating lost or damaged body parts. More research is needed to confirm the scientists’ findings, but of course BafA proteins will be of immense interest to the scientific community.
Dr. Yohei Doi from Fujita Health University
Yohei Doi, MD, Ph.D., is a professor in the Microbiology and Infectious Diseases Departments of the Medical School at Fujita Health University and director of the Center for Innovative Antimicrobial Therapy at the University of Pittsburgh. He has written 226 publications and worked in the editorial offices of several magazines. He is leading a clinical trial of the flu drug “Avigan” (favipiravir) as a potential treatment for COVID-19 at Fujita Health University.
Dr. Kentaro Tsukamoto from Fujita Health University
Kentaro Tsukamoto, DVM, Ph.D., is a Senior Assistant Professor in the Department of Microbiology in the Medical School of Fujita Health University. He has written 24 publications. His main research interests are bacteriology and host-pathogen interaction.
Fujita Health University
Fujita Health University is a private university in Toyoake, Aichi, Japan. Established in 1964, it is home to one of the largest teaching university hospitals in Japan in terms of the number of beds. With over 900 faculty members, the university strives to offer students a variety of academic opportunities at an international level. Fujita Health University ranks eighth among all universities and second among all private universities in Japan in the world rankings of 2020 Times Higher Education (THE). THE University Impact Rankings 2019 visualized university initiatives for Sustainable Development Goals (SDGs). For the SDG “Good Health and Wellbeing”, Fujita Health University was ranked second among all universities and first among private universities in Japan. The university will also be the first Japanese university to host THE Asia Universities Summit in June 2021. The founding philosophy of the university is “Our creativity for the people (DOKUSOU-ICHIRI)”, which reflects the conviction that, as at the university, alumni and alumnae, current students, also develop their future by using their creativity. https://www.fujita-hu.ac.jp/en/index.html
Financing information
This work was supported by JSPS KAKENHI Grant Number JP19K07548 (KT), MEXT-supported program for the Strategic Research Foundation at Private Universities of the Japanese Ministry of Education, Culture, Sports, Science and Technology (H. Kurahashi) and the grant for joint research project of Osaka University’s Research Institute for Microbial Diseases (KT).
reference
Title of the original work: The Bartonella car transporter BafA activates the host’s VEGF pathway to promote angiogenesis
Journal: Nature Communications
DOI: 10.1038 / s41467-020-17391-2
(i) Source / Reference: Fujita Health University, Japan. Disabled World makes no guarantees or warranties in connection therewith. Content may have been edited for style, clarity, or length.
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Journal: Disabled World. Language: English. Author: Fujita Health University, Japan. Electronic publication date: 2020-07-22. Last revised date: 2020-07-22. Reference title: “BafA stimulates the production of new blood vessels”, source: BafA stimulates the production of new blood vessels. Summary: The study provides insights into the BafA protein, which can be further used in regenerative medicine to replace or regenerate lost or damaged body parts. Retrieved on December 19, 2018 from https://www.disabled-world.com/news/research/stemcells/bafa.php – reference category number: DW # 143-13862.
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