Using bacteria from Bartonelle henselae species, researchers from Goethe University, University Hospital Frankfurt, the Federal Paul Ehrlich Institute for Vaccines and Biomedicine in Langen and the University of Oslo demonstrated for the first time that antibodies can prevent certain surface proteins of bacterial pathogens from entering host cells. The results are important for the development of new drugs once morest highly resistant infectious agents.
Infections, especially those caused by highly resistant pathogens, pose a significant threat to human health. It is dangerous when pathogens manage to colonize the body and subsequently cause serious infections. The first step in such an infection is always the attachment of pathogens to the surface of host cells. From there, infections spread, resulting in, for example, infections of deeper tissue layers and organs.
A group of scientists around Professor Volkhard Kempf from the Institute for Microbiology and Hospital Hygiene at Frankfurt University Hospital have now succeeded in blocking this adhesion mechanism in a bacterium, thus preventing infection of host cells. To this end, the researchers examined the pathogen Bartonelle henselae, usually causing cat scratch disease. Transmitted by cats, the disease mainly affects young children, whose symptoms include swollen and hardened lymph nodes around the site of infection, usually from scratches or bites from infected cats.
Bartonelle the bacteria infect so-called endothelial cells, which line the blood vessels. Via their surface protein Bartonelle adhesin A (BadA), they attach to a protein (fibronectin) of the so-called “extracellular matrix”, a network of protein fibers that lie on top of endothelial cells.
To determine which parts of the BadA protein are important in the process of bacterial adhesion, the researchers equipped Bartonelle bacteria with various genetically modified BadA variants, among others, and then analyzed to what extent these variants were still able to bind fibronectin. Once it was clear which BadA segments were responsible for the binding, the team produced antibodies once morest them, using cell culture experiments to show for the first time that such antibodies can prevent infection by such bacteria.
Professor Volkhard Kempf explains: “Bartonelle henselae is not a very dangerous pathogen and in most cases cat scratch disease does not require any specific medical treatment. However, for us Bartonelle henselae is a very important model organism for much more dangerous pathogens such as Acinetobacter baumannii, a serious pathogen that usually causes wound infection or pneumonia and often shows resistance to several last-choice antibiotics. The BadA protein of Bartonelle henselae belongs to the so-called “trimeric autotransport adhesins”, which are also responsible for adhesion to human cells in Acinetobacter and a number of other pathogens. Drug blocking of these adhesins is therefore a new and promising future approach to combating dangerous bacterial infections.”
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