Using bacteria of the species Bartonella henselae, researchers from Goethe University, University Hospital Frankfurt, the Paul Ehrlich Federal Institute for Vaccines and Biomedicines Langen and the University of Oslo demonstrated for the first time that antibodies can prevent certain surface proteins of bacterial pathogens. entering host cells. The findings are important for the development of new drugs against highly resistant infectious agents.
Infections, especially those with highly resistant pathogens, represent a major threat to human health. It is dangerous when pathogens manage to colonize the body and subsequently cause serious infections. The first step in this infection always involves pathogens attaching to the surface of host cells. From there, the infections spread, leading to, for example, infections of deeper tissue layers and organs.
A group of scientists led by Professor Volkhard Kempf from the Institute of Microbiology and Hospital Hygiene at the University Hospital Frankfurt has now succeeded in blocking this adhesion mechanism in a bacterium, thereby preventing infection of host cells. For this purpose, the researchers examined the pathogen Bartonella henselae, which usually causes 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 after a scratch or bite injury caused by infected cats.
Bartonella bacteria infect the so-called endothelial cells, which cover the blood vessels. Through their surface protein Bartonella adhesin A (BadA), they bind to a protein (fibronectin) in the so-called “extracellular matrix”, a network of protein fibers found on top of cells. endothelial cells.
To determine which parts of the BadA protein are important in the bacterial adhesion process, the researchers equipped Bartonella bacteria with several genetically engineered BadA variants, among others, and then analyzed to what extent these variants were still capable of binding fibronectin. Once it became clear which BadA segments were responsible for binding, the team produced antibodies against them, using cell culture experiments to demonstrate for the first time that these antibodies can prevent infection by these bacteria.
Bartonella henselae is not a very dangerous pathogen and, in most cases, cat scratch disease does not require any specific medical treatment. However, for us Bartonella henselae is a very important model organism for much more dangerous pathogens such as Acinetobacter baumannii, a serious pathogen that often causes wound infection or pneumonia and often shows resistance to several last-line antibiotics. The BadA protein of Bartonella henselae belongs to the so-called “trimeric autotransporter adhesins”, which are also responsible for the adhesion to human cells of Acinetobacter and other pathogens. Therefore, a drug-induced blockade of these adhesins is a promising new and future approach to combat dangerous bacterial infections.”
Prof. Volkhard Kempf, Institute of Microbiology and Hospital Hygiene at the University Hospital of Frankfurt
The research was supported by the ViBrANT program (Viral and Bacterial Adhesin Network Training); a European Union HORIZON 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement; the Robert Koch Institute, Berlin, Germany; the “PROXYDRUGS” project of the Federal Ministry of Education and Research; as well as the German Research Foundation DFG.
Source:
Goethe University Frankfurt am Main
Journal reference:
Thibau, A., et al. (2022) Adhesion of Bartonella henselae to fibronectin is mediated by repetitive motifs present in the stalk of Bartonella Adhesin A. Microbiology Spectrum. doi.org/10.1128/spectrum.02117-22.