Antibodies can prevent bacterial surface proteins from entering host cells

Antibodies can prevent bacterial surface proteins from entering host cells

Using Bartonella henselae bacteria, scientists from Goethe University, Frankfurt University Hospital, the Paul Ehrlich Federal Institute for Vaccines and Biomedicine in Langen and the University of Oslo have shown for the first time that antibodies can prevent the formation of 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, pose a significant threat to human health. It is dangerous when pathogens manage to colonize the organism and subsequently cause severe infections. The first step in such an infection is always for pathogens to attach to the surface of host cells. From there, the infection spreads, resulting in, for example, infections of deeper layers of tissues and organs.

A group of scientists around prof. Volkhard Kempf from the Institute of Microbiology and Hospital Hygiene of the University Hospital in Frankfurt has now succeeded in blocking this adhesion mechanism in the bacterium, thus preventing infection of host cells. For this purpose, the scientists studied the pathogen Bartonella henselae, usually causes cat scratch disease. The cat-borne disease mainly affects young children, whose symptoms include swollen and hardened lymph nodes around the site of infection – usually after a scratch or bite from an infected cat.

Bartonella the bacteria infect the so-called endothelial cells that line the blood vessels. Through their surface protein Bartonella adhesin A (BadA), attach to a protein (fibronectin) of the so-called “extracellular matrix”, a network of protein fibers that lies on the surface of endothelial cells.

For the researchers to determine which parts of the BadA protein are important in the bacterial adhesion process Bartonella bacteria with different genetically modified variants of BadA, among others, and then analyzed to what extent these variants were still able to bind fibronectin. Once it was clear which segments of BadA were responsible for binding, the team made antibodies against them using cell culture experiments to show for the first time that such antibodies could prevent infection by such 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 far more dangerous pathogens such as Acinetobacter baumannii, a serious pathogen that usually causes wound infection or pneumonia and often shows resistance to several last-line antibiotics. BadA protein Bartonella henselae is among the so-called “trimeric autotransporter adhesins” that are also responsible for adhesion to human cells in Acinetobacter and a number of other pathogens. Drug-induced blocking of these adhesins is therefore a promising new and future approach to combat dangerous bacterial infections.”

Prof. Volkhard Kempf, Institute of Microbiology and Hospital Hygiene, University Hospital Frankfurt

The research was supported by the ViBrANT program (Viral and Bacterial Adhesin Network Training); the research and innovation program of the European Union HORIZON 2020 within the Marie Skłodowska-Curie grant agreement; 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 in Frankfurt am Main

Link to journal:

Thibau, A., et al. (2022) Adhesion of Bartonella henselae to fibronectin is mediated by repetitive motifs present in the stem of Bartonella adhesin A. Microbiological spectrum. doi.org/10.1128/spectrum.02117-22.

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