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
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
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.
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.
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
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
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".
Professor Volkhard A. J. Kempf
Director of the Institute of Medical Microbiology and Hospital Hygiene
University Hospital Frankfurt
Tel.: +49 (0)69 6301–5019