Press releases – 2022– Search

Using bacteria of the Bartonella henselae species, researchers from Goethe University, Frankfurt University Hospital, the Paul Ehrlich Federal Institute for Vaccines and Biomedicines 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 findings are important for the development of new drugs against highly resistant infectious agents.

FRANKFURT. 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 always consists of the pathogens attaching themselves to the host cells' surface. From here, the infections spread, resulting, for example, in infections of deeper tissue layers and organs.

A group of scientists surrounding Prof. Volkhard Kempf from Frankfurt University Hospital's Institute of Microbiology and Hospital Hygiene has now succeeded in blocking this adhesion mechanism in a bacterium, thereby preventing the infection of host cells. For this purpose, the researchers examined the pathogen Bartonella 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 following a scratch or bite injury caused by infected cats.

Bartonella bacteria infect so-called endothelial cells, which line the blood vessels. Via their surface protein Bartonella adhesin A (BadA), they attach themselves to a protein (fibronectin) of the so-called "extracellular matrix", a network of protein fibers that lie on top of the endothelial cells.

To determine which parts of the BadA protein are important in the bacterial adhesion process, the researchers equipped Bartonella bacteria with various genetically modified BadA variants, among others, and then analyzed the extent to which these variants were still able to bind fibronectin. Once it was clear which BadA segments were responsible for the binding, the team produced antibodies against them, using cell culture experiments to show for the first time that such antibodies can prevent infection by such bacteria.

Prof. Volkhard Kempf explains: "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-choice antibiotics. The BadA protein of Bartonella henselae belongs to the so-called 'trimeric autotransporter adhesins', which are also responsible for adhesion to human cells in Acinetobacter and a number of other pathogens. A drug-induced blocking of these adhesins is therefore a promising novel and future approach to combat dangerous bacterial infections."

The research was supported by the Viral and Bacterial Adhesin Network Training (ViBrANT) program; a HORIZON 2020 research and innovation program of the European Union 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.

Publication: Arno Thibau, Diana J. Vaca, Marlene Bagowski, Katharina Hipp, Daniela Bender, Wibke Ballhorn, Dirk Linke, Volkhard A. J. Kempf: Adhesion of Bartonella henselae to Fibronectin Is Mediated via Repetitive Motifs Present in the Stalk of Bartonella Adhesin A. https://journals.asm.org/doi/10.1128/spectrum.02117-22

Background: How bacteria adhere to cells: Basis for the development of a new class of antibiotics (22 June 2022) https://www.goethe-university-frankfurt.de/74958144?search=kempf

Picture download:
https://www.kgu.de/fileadmin/redakteure/Presse/Bilder_Pressmitteilungen/2022/Bartonella_henselae.jpg

Caption: Adhesion of Bartonella henselae (blue) to human blood vessel cells (red). The bacterium's adhesion to the host cells could be blocked with the help of so-called “anti-ligands". Credit: https://www.mdpi.com/2075-4418/11/7/1259

Further information:
Professor Volkhard A. J. Kempf
Director of the Institute of Medical Microbiology and Hospital Hygiene
University Hospital Frankfurt
Goethe University Frankfurt
Phone: +49 (0)69 6301–5019
volkhard.kempf@kgu.de
Website: https://www.kgu.de/einrichtungen/institute/zentrum-der-hygiene/medizinische-mikrobiologie-und-krankenhaushygiene

Researchers from University Hospital Frankfurt and Goethe University Frankfurt have unravelled how bacteria adhere to host cells and thus taken the first step towards developing a new class of antibiotics.

FRANKFURT. The adhesion of bacteria to host cells is always the first and one of the decisivesteps in the development of infectious diseases. The purpose of this adhesion by infectious pathogens is first to colonize the host organism (i.e., the human body), and then to trigger an infection, which in the worst case can end fatally. Precise understanding of the bacteria's adhesion to host cells is a key to finding therapeutic alternatives that block this critical interaction in the earliest possible stage of an infection.

Critical interaction with the human protein fibronectin
In collaboration with other researchers, scientists from University Hospital Frankfurt and Goethe University Frankfurt have now explained the exact bacterial adhesion mechanism using the human-pathogenic bacterium Bartonella henselae. This pathogen causes “cat-scratch disease", a disease transmitted from animals to humans. In an international collaborative project led by the Frankfurt research group headed by Professor Volkhard Kempf, the bacterial adhesion mechanism was deciphered with the help of a combination of in-vitro adhesion tests and high-throughput proteomics. Proteomics is the study of all the proteins present in a cell or a complex organism.

The scientists have shed light on a key mechanism: the bacterial adhesion to the host cells can be traced back to the interaction of a certain class of adhesins – called “trimeric autotransporter adhesins" – with fibronectin, a protein often found in human tissue. Adhesins are components on the surface of bacteria which enable the pathogen to adhere to the host's biological structures. Homologues of the adhesin identified here as critical are also present in many other human-pathogenic bacteria, such as the multi-resistant Acinetobacter baumannii, which the World Health Organization (WHO) has classified as the top priority for research into new antibiotics.

State-of-the-art protein analytics were used to visualize the exact points of interaction between the proteins. In addition, it was possible to show that experimental blocking of these processes almost entirely prevents bacterial adhesion. Therapeutic approaches that aim to prevent bacterial adhesion in this way could represent a promising treatment alternative as a new class of antibiotics (known as “anti-ligands") in the constantly growing domain of multi-resistant bacteria.

Prestigious funding
The research work was funded as part of an Innovative Training Network (“ViBrANT: Viral and Bacterial Adhesin Network Training") under the Marie Skłodowska-Curie Actions (MSCA) of the European Union's HORIZON 2020 research and innovation programme.

The scientific paper has been published in the prestigious journal “Microbiology Spectrum" of the American Society of Microbiology (ASM) and was acknowledged as “Paper of the Month" by the German Society for Hygiene and Microbiology (DGHM) on 18 June 2022.

Publication: Vaca, D. J., Thibau, A., Leisegang, M. S., Malmström, J., Linke, D., Eble, J. A., Ballhorn, W., Schaller, M., Happonen, L., Kempf, V. A. J.; Interaction of Bartonella henselae with Fibronectin Represents the Molecular Basis for Adhesion to Host Cells; Microbiology Spectrum, 18 April, 2022. https://doi.org/10.1128/spectrum.00598-22

Picture download:
https://www.kgu.de/fileadmin/redakteure/Presse/Bilder_Pressmitteilungen/2022/Vaca_Diana_Jaqueline.jpgCaption: First author of the study: Diana Jaqueline Vaca, Institute of Medical Microbiology and Hospital Hygiene at University Hospital Frankfurt. Photo: University Hospital Frankfurt

https://www.kgu.de/fileadmin/redakteure/Presse/Bilder_Pressmitteilungen/2022/Bartonella_henselae.jpg
Adhesion of Bartonella henselae (blue) to human blood vessel cells (red). The bacterium's adhesion to the host cells could be blocked with the help of what are known as “anti-ligands".

Credit: https://www.mdpi.com/2075-4418/11/7/1259

Further information:
Professor Volkhard A. J. Kempf
Director of the Institute of Medical Microbiology and Hospital Hygiene
University Hospital Frankfurt
Tel.: +49 (0)69 6301–5019
volkhard.kempf@kgu.de
Website: https://www.kgu.de/einrichtungen/institute/zentrum-der-hygiene/medizinische-mikrobiologie-und-krankenhaushygiene

Editor: Christoph Lunkenheimer, Press Officer, Staff Unit Communication at Universitätsklinikum Frankfurt, Phone: +49 (0)69 6301–86442, christoph.lunkenheimer@kgu.de