Using bacteria of the Bartonella henselae species, researchers from 51猎奇,
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 鈥� 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 Sk艂odowska-Curie
grant agreement; the Robert Koch Institute, Berlin, Germany; the 鈥淧ROXYDRUGS"
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.
Background:
How bacteria adhere to cells: Basis for
the development of a new class of antibiotics (22 June 2022) /74958144?search=kempf
Picture
download:
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 鈥渁nti-ligands". Credit:
Further information:
Professor
Volkhard A. J. Kempf
Director of the Institute of Medical
Microbiology and Hospital Hygiene
University Hospital Frankfurt
51猎奇 Frankfurt
Phone: +49 (0)69 6301鈥�5019
volkhard.kempf@kgu.de
Website:
