{"id":3555,"date":"2020-07-15T15:10:40","date_gmt":"2020-07-15T15:10:40","guid":{"rendered":"https:\/\/www.editage.com\/insights\/how-a-parasitic-bacterium-induces-blood-vessel-formation-to-cause-lesions\/"},"modified":"2025-01-15T06:29:47","modified_gmt":"2025-01-15T06:29:47","slug":"how-a-parasitic-bacterium-induces-blood-vessel-formation-to-cause-lesions","status":"publish","type":"post","link":"https:\/\/www.editage.com\/insights\/how-a-parasitic-bacterium-induces-blood-vessel-formation-to-cause-lesions","title":{"rendered":"How a parasitic bacterium induces blood vessel formation to cause lesions"},"content":{"rendered":"<p style=\"text-align:justify; margin:0in 0in 0.0001pt\"><span style=\"font-size:12pt\"><span style=\"text-justify:inter-ideograph\"><span style=\"font-family:&quot;Times New Roman&quot;,serif\"><span style=\"font-family:&quot;Calibri&quot;,sans-serif\">Bacteria of the genus <em>Bartonella<\/em> are\u00a0parasites that can be transmitted to humans via insect bites and animal scratches, resulting in an infection known as \u201cbartonellosis.\u201d Cat-scratch disease and trench fever are forms of bartonellosis caused by different <i>Bartonella <\/i>species infecting humans. <i>Bartonella <\/i>bacteria can cause lesions to pop up in the skin and internal organs. To provide themselves with a safe habitat, the bacteria bring about the increase of the number of \u201cvascular endothelial\u201d cells (cells that line the interior of blood vessels), which hide themselves from the host immune system and stimulate the creation of new blood vessels, through a process called \u201cangiogenesis.\u201d <\/span><\/span><\/span><\/span><\/p>\n<p style=\"text-align:justify; margin:0in 0in 0.0001pt\">\u00a0<\/p>\n<p style=\"text-align:justify; margin:0in 0in 0.0001pt\"><span style=\"font-size:12pt\"><span style=\"text-justify:inter-ideograph\"><span style=\"font-family:&quot;Times New Roman&quot;,serif\"><span style=\"font-family:&quot;Calibri&quot;,sans-serif\">Previous studies on <em>Bartonella henselae<\/em><i> <\/i>(<i>B. henselae<\/i> for short), the bacterium responsible for cat-scratch disease, have shown that it can directly \u201cinject\u201d proteins that inhibit programmed cell death (apoptosis) into the endothelial cells. However, B<em>. henselae<\/em> can also promote angiogenesis without directly contacting endothelial cells, which implies that the bacterium can secrete a bioactive substance that takes on the duty of kick-starting angiogenesis. <\/span><\/span><\/span><\/span><\/p>\n<p style=\"text-align:justify; margin:0in 0in 0.0001pt\">\u00a0<\/p>\n<p style=\"text-align:justify; margin:0in 0in 0.0001pt\"><span style=\"font-size:12pt\"><span style=\"text-justify:inter-ideograph\"><span style=\"font-family:&quot;Times New Roman&quot;,serif\"><span style=\"font-family:&quot;Calibri&quot;,sans-serif\">In a <a href=\"https:\/\/doi.org\/10.1038\/s41467-020-17391-2\" style=\"color:blue; text-decoration:underline\">new study published in <i>Nature Communications<\/i><\/a>, a team of scientists led by Senior Assistant Professor Kentaro Tsukamoto and Professor Yohei Doi of Fujita Health University, Japan, have identified that this bioactive substance is actually a protein. They have also named this protein as <i>Bartonella <\/i>angiogenic factor A, or \u201cBafA\u201d for short. This is the very first report of a vascular endothelial growth factor (VEGF for short)-like protein produced by bacteria.<\/span><\/span><\/span><\/span><\/p>\n<p style=\"margin:0in 0in 0.0001pt\">\u00a0<\/p>\n<p style=\"text-align:justify; margin:0in 0in 0.0001pt\"><span style=\"font-size:12pt\"><span style=\"text-justify:inter-ideograph\"><span style=\"font-family:&quot;Times New Roman&quot;,serif\"><span style=\"font-family:&quot;Calibri&quot;,sans-serif\">The scientists started their project by introducing<i> B. henselae <\/i>into human endothelial cells in petri dishes, and observed that the bacteria caused the endothelial cells to multiply. To identify the genes that give <i>B. henselae<\/i> this ability, the researchers began inducing random mutations in the DNA of the bacteria and seeing whether the mutated bacteria could still make the endothelial cells multiply. Through these experiments, the scientists determined that <i>B. henselae<\/i> can stimulate angiogenesis in human endothelial cells only if it possesses a functional copy of the gene that \u201ccodes for,\u201d or guides the synthesis of, the BafA protein. They also observed that exposing human endothelial cells to the isolated BafA protein caused the cells to multiply.\u00a0 <\/span><\/span><\/span><\/span><\/p>\n<p style=\"text-align:justify; margin:0in 0in 0.0001pt\">\u00a0<\/p>\n<p style=\"text-align:justify; margin:0in 0in 0.0001pt\"><span style=\"font-size:12pt\"><span style=\"text-justify:inter-ideograph\"><span style=\"font-family:&quot;Times New Roman&quot;,serif\"><span style=\"font-family:&quot;Calibri&quot;,sans-serif\">Then, to confirm that BafA stimulates angiogenesis, the scientists extracted samples of a major blood vessel called the aorta from mice and placed the samples in gels that did or did not contain BafA. As can be seen in the image below, the aorta samples that were not exposed to BafA did not sprout new blood vessels, but the aorta samples that were exposed to BafA grew vessels that extended into the gel. The scientists also found that surgically placing a BafA-containing gel plug into living mice led to blood vessels growing from the surrounding tissue into the gel. <\/span><\/span><\/span><\/span><\/p>\n<p style=\"text-align:justify; margin:0in 0in 0.0001pt\">\u00a0<\/p>\n<p style=\"text-align:justify; margin:0in 0in 0.0001pt\"><span style=\"font-size:12pt\"><span style=\"text-justify:inter-ideograph\"><span style=\"font-family:&quot;Times New Roman&quot;,serif\"><span style=\"font-family:&quot;Calibri&quot;,sans-serif\">Further experiments with human endothelial cells in petri dishes indicated that BafA activated cell surface receptors that recognize VEGF. By binding to these receptors, BafA triggered the activation of a process inside the cells, involving proteins called mitogen-activated protein kinase (MAPK) and extracellular signal\u2013regulated kinases (ERKs). The MAPK\/ERK pathway plays an important role in the multiplication of endothelial cells and angiogenesis. <i>\u201cIn 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,<\/i>\u201d explains Dr Tsukamoto.<\/span><\/span><\/span><\/span><\/p>\n<p style=\"text-align:justify; margin:0in 0in 0.0001pt\">\u00a0<\/p>\n<p style=\"text-align:justify; margin:0in 0in 0.0001pt\"><span style=\"font-size:12pt\"><span style=\"text-justify:inter-ideograph\"><span style=\"font-family:&quot;Times New Roman&quot;,serif\"><span style=\"font-family:&quot;Calibri&quot;,sans-serif\">These findings provide valuable insights into the mechanisms by which infectious bacteria can produce lesions in their hosts. <i>\u201cWe believe that BafA proteins can be leveraged as tools for studying angiogenesis, and we also consider potential medical benefits,<\/i>\u201d reports Prof Doi. \u201c<i>Most importantly,\u201d<\/i> he elaborates, <i>\u201cBafA is a potential target for the development of diagnostic and therapeutic strategies for bartonellosis.\u201d<\/i> <\/span><\/span><\/span><\/span><\/p>\n<p style=\"text-align:justify; margin:0in 0in 0.0001pt\">\u00a0<\/p>\n<p style=\"text-align:justify; margin:0in 0in 0.0001pt\"><span style=\"font-size:12pt\"><span style=\"text-justify:inter-ideograph\"><span style=\"font-family:&quot;Times New Roman&quot;,serif\"><span style=\"font-family:&quot;Calibri&quot;,sans-serif\">The scientists also speculate that BafA proteins could be used in regenerative medicine, which is a highly specialized branch of medicine that deals with replacing or regenerating lost or damaged parts of the body. Further research is needed to confirm the scientists\u2019 findings, but needless to say, BafA proteins will certainly be of immense interest to the scientific community.<\/span><\/span><\/span><\/span><\/p>\n<p style=\"text-align:justify; margin:0in 0in 0.0001pt\">\u00a0<\/p>\n<p style=\"margin:0in 0in 0.0001pt\"><span style=\"font-size:12pt\"><span style=\"font-family:&quot;Times New Roman&quot;,serif\"><b><span style=\"font-family:&quot;Calibri&quot;,sans-serif\">Reference<\/span><\/b><\/span><\/span><\/p>\n<p style=\"margin:0in 0in 0.0001pt\"><span style=\"font-size:12pt\"><span style=\"tab-stops:130.5pt\"><span style=\"font-family:&quot;Times New Roman&quot;,serif\"><span style=\"font-size:11.0pt\"><span style=\"font-family:&quot;Calibri&quot;,sans-serif\">Title of original paper: The <i>Bartonella <\/i>autotransporter BafA activates the host VEGF pathway to drive angiogenesis<\/span><\/span><\/span><\/span><\/span><\/p>\n<p style=\"margin:0in 0in 0.0001pt\"><span style=\"font-size:12pt\"><span style=\"tab-stops:130.5pt\"><span style=\"font-family:&quot;Times New Roman&quot;,serif\"><span style=\"font-size:11.0pt\"><span style=\"font-family:&quot;Calibri&quot;,sans-serif\">Journal: <i>Nature Communications<\/i><\/span><\/span><\/span><\/span><\/span><\/p>\n<p style=\"margin:0in 0in 0.0001pt\"><span style=\"font-size:12pt\"><span style=\"tab-stops:130.5pt\"><span style=\"font-family:&quot;Times New Roman&quot;,serif\"><span style=\"font-size:11.0pt\"><span style=\"font-family:&quot;Calibri&quot;,sans-serif\">DOI:\u00a0<a href=\"https:\/\/doi.org\/10.1038\/s41467-020-17391-2\" style=\"color:blue; text-decoration:underline\">10.1038\/s41467-020-17391-2<\/a> <\/span><\/span><\/span><\/span><\/span><\/p>\n<p class=\"Default\" style=\"margin:0in 0in 0.0001pt\">\u00a0<\/p>\n<p class=\"Default\" style=\"margin:0in 0in 0.0001pt\"><span style=\"font-size:12pt\"><span style=\"font-family:Calibri,sans-serif\"><span style=\"color:black\"><b>About Fujita Health University<\/b><\/span><\/span><\/span><\/p>\n<p style=\"text-align:justify; margin:0in 0in 0.0001pt\"><span style=\"font-size:12pt\"><span style=\"text-justify:inter-ideograph\"><span style=\"font-family:&quot;Times New Roman&quot;,serif\"><span style=\"font-family:&quot;Calibri&quot;,sans-serif\"><a href=\"https:\/\/www.fujita-hu.ac.jp\/en\/index.html\">Fujita Health University<\/a> is a private university situated in Toyoake, Aichi, Japan. It was founded in 1964 and houses one of the largest teaching university hospitals in Japan in terms of the number of beds. With over 900 faculty members, the university is committed to providing various academic opportunities to students internationally. Fujita Health University has been ranked eighth among all universities and second among all private universities in Japan in the 2020 Times Higher Education (THE) World University Rankings. THE University Impact Rankings 2019 visualized university initiatives for sustainable development goals (SDGs). For the \u201cgood health and well-being\u201d SDG, Fujita Health University was ranked second among all universities and number one among private universities in Japan. The university will also be the first Japanese university to host the &#8220;THE Asia Universities Summit&#8221; in June 2021. The university\u2019s founding philosophy is \u201cOur creativity for the people (DOKUSOU-ICHIRI),\u201d which reflects the belief that, as with the university\u2019s alumni and alumnae, current students also unlock their future by leveraging their creativity.<\/span><\/span><\/span><\/span><\/p>\n<p style=\"text-align:justify; margin:0in 0in 0.0001pt\">\u00a0<\/p>\n<p class=\"Default\" style=\"margin:0in 0in 0.0001pt\"><span style=\"font-size:12pt\"><span style=\"font-family:Calibri,sans-serif\"><span style=\"color:black\"><b>About Dr Yohei Doi from Fujita Health University<\/b><\/span><\/span><\/span><\/p>\n<p class=\"Default\" style=\"margin:0in 0in 0.0001pt\"><span style=\"font-size:12pt\"><span style=\"font-family:Calibri,sans-serif\"><span style=\"color:black\">Yohei Doi,\u00a0M.D., Ph.D., is a Professor at the Departments of Microbiology and Infectious Diseases at Fujita Health University School of Medicine and the Director of the Center for Innovative Antimicrobial Therapy at the University of Pittsburgh. He has authored 226 publications and has served on several journals\u2019 editorial boards. He is leading a clinical trial of the flu drug \u201cAvigan\u201d (favipiravir) as a potential treatment for COVID-19 at Fujita Health University. <\/span><\/span><\/span><\/p>\n<p class=\"Default\" style=\"margin:0in 0in 0.0001pt\">\u00a0<\/p>\n<p class=\"Default\" style=\"margin:0in 0in 0.0001pt\"><span style=\"font-size:12pt\"><span style=\"font-family:Calibri,sans-serif\"><span style=\"color:black\"><b>About Dr Kentaro Tsukamoto from Fujita Health University<\/b><\/span><\/span><\/span><\/p>\n<p class=\"Default\" style=\"margin:0in 0in 0.0001pt\"><span style=\"font-size:12pt\"><span style=\"font-family:Calibri,sans-serif\"><span style=\"color:black\">Kentaro Tsukamoto, D.V.M., Ph.D., is a Senior Assistant Professor in the Department of Microbiology at Fujita Health University School of Medicine. He has authored 24 publications. His areas of research interest include bacteriology and host-pathogen interaction.<\/span><\/span><\/span><\/p>\n<p class=\"Default\" style=\"margin:0in 0in 0.0001pt\">\u00a0<\/p>\n<p class=\"Default\" style=\"margin:0in 0in 0.0001pt\"><span style=\"font-size:12pt\"><span style=\"font-family:Calibri,sans-serif\"><span style=\"color:black\"><b>Funding information<\/b><\/span><\/span><\/span><\/p>\n<p class=\"Default\" style=\"margin:0in 0in 0.0001pt\"><span style=\"font-size:12pt\"><span style=\"font-family:Calibri,sans-serif\"><span style=\"color:black\">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.).<\/span><\/span><\/span><\/p>\n<p class=\"Default\" style=\"margin:0in 0in 0.0001pt\">\u00a0<\/p>\n<p style=\"margin:0in 0in 0.0001pt\"><span style=\"font-size:12pt\"><span style=\"font-family:&quot;Times New Roman&quot;,serif\"><b><span style=\"font-family:&quot;Calibri&quot;,sans-serif\">Media contact: \u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 <\/span><\/b><\/span><\/span><\/p>\n<p style=\"margin:0in 0in 0.0001pt\"><span style=\"font-size:12pt\"><span style=\"font-family:&quot;Times New Roman&quot;,serif\"><span style=\"font-size:11.0pt\"><span style=\"font-family:&quot;Calibri&quot;,sans-serif\">Dr Kentaro Tsukamoto<\/span><\/span><\/span><\/span><\/p>\n<p style=\"margin-left:.9pt; margin:0in 0in 0.0001pt\"><span style=\"font-size:12pt\"><span style=\"tab-stops:131.15pt\"><span style=\"font-family:&quot;Times New Roman&quot;,serif\"><span class=\"MsoHyperlink\" style=\"color:blue\"><span style=\"text-decoration:underline\"><span style=\"font-size:11.0pt\"><span style=\"font-family:&quot;Calibri&quot;,sans-serif\"><a href=\"mailto:tsuka-k@fujita-hu.ac.jp\" style=\"color:blue; text-decoration:underline\">tsuka-k@fujita-hu.ac.jp<\/a><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/p>\n","protected":false},"excerpt":{"rendered":"<p>Bacteria of the genus Bartonella are\u00a0parasites that can be transmitted to humans via insect bites and animal scratches, resulting in an infection known as \u201cbartonellosis.\u201d Cat-scratch disease and trench fever are forms of bartonellosis caused by different Bartonella species infecting humans. Bartonella bacteria can cause lesions to pop up in the skin and internal organs. [&hellip;]<\/p>\n","protected":false},"author":1152,"featured_media":33313,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"inline_featured_image":false,"footnotes":""},"categories":[2435],"tags":[2482],"new_categories":[],"new_tags":[],"series":[],"class_list":["post-3555","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-trending-research","tag-science-update"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v25.0 - https:\/\/yoast.com\/wordpress\/plugins\/seo\/ -->\n<title>How a parasitic bacterium induces blood vessel formation to cause lesions | Editage Insights<\/title>\n<meta name=\"description\" content=\"Researchers from Fujita Health University found the bacteria Bartonella release a protein that stimulates the production of new blood vessels that support bacterial lesions, which may help scientists develop new methods for 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