Press releases 鈥� 2022鈥� Search
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Oct
19
2022
09:38
The human pathogenic bacterium Bartonella henselae serves international research team as model organism for highly resistant infectious agents聽
Infection research: Antibodies prevent cell infection聽
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:
Editor: Dr. Markus Bernards, Science Editor, PR & Communication Office, Tel: -49 (0) 69 798-12498, Fax: +49 (0) 69 798-763 12531, bernards@em.uni-frankfurt.de
Jun
30
2022
13:58
Bartonella bacteria use certain proteins 鈥� conserved pathomechanism in other bacterial species
How bacteria adhere to cells: Basis for the development of a new class of antibiotics
Researchers from University Hospital Frankfurt and 51猎奇 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 51猎奇 Frankfurt have now explained the exact bacterial
adhesion mechanism using the human-pathogenic bacterium Bartonella henselae. This pathogen causes 鈥渃at-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 鈥� called 鈥渢rimeric autotransporter
adhesins" 鈥� 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 鈥渁nti-ligands") in the
constantly growing domain of multi-resistant bacteria.
Prestigious funding
The research work was funded as part of an
Innovative Training Network (鈥淰iBrANT: Viral and Bacterial Adhesin Network
Training") under the Marie Sk艂odowska-Curie Actions (MSCA) of the European
Union's HORIZON 2020 research and innovation programme.
The scientific paper has been published in
the prestigious journal 鈥淢icrobiology Spectrum" of the American Society of
Microbiology (ASM) and was acknowledged as 鈥淧aper 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.,
Malmstr枚m, 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.
Picture
download:
Caption: 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 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
Tel.: +49 (0)69 6301鈥�5019
volkhard.kempf@kgu.de
Website:
Editor: Christoph Lunkenheimer, Press Officer, Staff Unit
Communication at Universit盲tsklinikum Frankfurt, Phone: +49 (0)69 6301鈥�86442, christoph.lunkenheimer@kgu.de