Tsukamoto Lab／International Research Center for Infectious Diseases  Laboratory of Bacterial Zoonoses

Zoonoses are infectious diseases caused by pathogens, including bacteria, viruses, and parasites, transmitted between vertebrate animals and humans. Among the zoonotic pathogens, some exhibit no virulence in animals but can cause diseases in humans. What factors give rise to such host specificity? Reaching a conclusive answer is not straightforward because of the variety of factors among pathogens and the intricate interplay of host factors. Our research group focuses on zoonotic bacteria, aiming to uncover the molecular mechanisms of their pathogenicity and symbiosis. Through our studies, we aim to unravel the enigma of host specificity associated with these bacteria.

Understanding the mechanism of Bartonella infection and pathogenesis

Bacteria classified under the genus Bartonella inhabit a variety of mammals and blood-sucking arthropods, and over 40 species have been identified to date. Among them, the most well-known is Bartonella henselae, the causative agent of cat-scratch disease. As a natural reservoir host, this microbe primarily resides in cats, with carrier cats remaining asymptomatic; however, human infection results in lymphadenopathy with fever. Some species other than B. henselae are pathogenic in humans. We are exploring the factors associated with the infectivity and pathogenicity of these various Bartonella species. By using human cells and tissue models, we are making progress with elucidation of the molecular mechanisms involved in disease initiation.

Angiogenic factor produced by Bartonella

Upon infecting humans, Bartonella targets and invades endothelial cells. Additionally, this bacterium stimulates angiogenesis by promoting the growth of endothelial cells. In other words, Bartonella has the inherent ability to stimulate the proliferation of endothelial cells, which serve as the replicative niche, potentially contributing to the establishment of infection and the manifestation of pathogenicity. We have identified a protein named BafA, which is released by the bacteria and is directly involved in inducing angiogenesis. BafA interacts with vascular endothelial growth factor receptor, which is located on the surface of human endothelial cells, leading to endothelial cell proliferation and angiogenesis. We are currently analyzing the molecular structure and mechanism of action of BafA, with the aim of elucidating how it is implicated in bacterial infectivity and pathogenicity.