Press releases 鈥� June 2022
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
Jun
3
2022
08:02
German-American research team deciphers evolution of pathogenic Acinetobacter strains
Genetics: How a harmless environmental bacterium became the dreaded hospital germ Acinetobacter baumannii
Hospital-acquired infections (HAIs) are often particularly difficult to treat because the pathogens have developed resistance to common antibiotics. The bacterium Acinetobacter baumannii is particularly dreaded in this respect, and research is seeking new therapeutic approaches to combat it. To look for suitable starting points, an international team led by bioinformaticians at 51猎奇 Frankfurt has compared thousands of genomes of pathogenic and harmless Acinetobacter strains. This has delivered clues about which properties might have made A. baumannii a successful pathogen 鈥� and how it might possibly be combated.
FRANKFURT/ST.
LOUIS. Each year, over 670,000 people in Europe fall ill
through pathogenic bacteria that exhibit antibiotic resistance, and 33,000 die
of the diseases they cause. Especially feared are pathogens that are resistant
to several antibiotics at the same time. Among them is the bacterium Acinetobacter baumannii, which is today
dreaded above all as a 鈥渉ospital superbug": up to five percent of all
hospital-acquired bacterial infections are caused by this germ alone.
A. baumannii is right at the top of a list of candidates for
which, according to the World Health Organization (WHO), new therapies must be
developed. This is because the pathogen 鈥� due to a flexible genome 鈥� easily
acquires new antibiotic resistance. At the same time, infections are not only occurring
more and more outside the hospital environment but also leading to increasingly
severe progression. However, a prerequisite for the
development of new therapeutic approaches is that we understand which
properties make A. baumannii and its human pathogenic relatives, grouped
in what is known as the Acinetobacter calcoaceticus-baumannii (ACB) complex,
a pathogen.
A team led by bioinformatician Professor
Ingo Ebersberger from 51猎奇 Frankfurt/ LOEWE Centre for
Translational Biodiversity Genomics (LOEWE-TBG) has now reached a milestone in
this understanding. The team is composed of members of Research Unit 2251 of
the German Research Foundation and other national and international partners,
among them scientists of Washington University School of Medicine, St Louis,
USA.
For their analysis, the team made use of
the fact that a large proportion of the members of the Acinetobacter
genus are harmless environmental bacteria that live in water or on plants or
animals. Thousands of complete genome sequences both of these as well as of
pathogenic Acinetobacter strains are stored in publicly accessible
databases.
By comparing these genomes, the
researchers were able to systematically filter out differences between the
pathogenic and the harmless bacteria. Because the incidence of individual genes
was not particularly conclusive, Ebersberger and his colleagues concentrated on
gene clusters, that is, groups of neighbouring genes that have remained stable
during evolution and might form a functional unit. 鈥淥f these evolutionarily
stable gene clusters, we identified 150 that are present in pathogenic Acinetobacter
strains and rare or absent in their non-pathogenic relatives," says
Ebersberger, summing up. 鈥淚t is highly probable that these gene clusters benefit
the pathogens' survival in the human host."
Among the most important properties of
pathogens is their ability to form protective biofilms and to efficiently
absorb micronutrients such as iron and zinc. And indeed, the researchers
discovered that the uptake systems in the ACB group were a reinforcement of the
existing and evolutionary older uptake mechanism.
Particularly exciting is the fact that the
pathogens have evidently tapped a special source of energy: they can break down
the carbohydrate kynurenine produced by humans, which as a messenger substance regulates
the innate immune system. The bacteria apparently kill two birds with one stone
in this way. On the one hand, breaking down kynurenine supplies them with
energy, and on the other hand, they could possibly use it to deregulate the
host's immune response.
Ebersberger is convinced: 鈥淥ur work is a
milestone in understanding what's different about pathogenic Acinetobacter
baumannii. Our data are of such a high resolution that we can even look at
the situation in individual strains. This knowledge can now be used to develop
specific therapies against which, with all probability, resistance does not yet
exist."
Publication:
Bardya Djahanschiri, Gisela Di Venanzio,
Jesus S. Distel, Jennifer Breisch, Marius Alfred Dieckmann, Alexander Goesmann,
Beate Averhoff, Stephan G枚ttig, Gottfried Wilharm, Mario F. Feldman, Ingo
Ebersberger: Evolutionarily stable gene
clusters shed light on the common grounds of pathogenicity in the Acinetobacter
calcoaceticus-baumannii complex. PLOS Genetics (2022) DOI:
10.1371/journal.pgen.1010020
Picture
download:
Acinetobacter baumannii
Scanning electron micrograph of a cluster
of Gram-negative, immobile bacteria of the Acinetobacter
baumannii species. Photo:
Janice Carr
Further
information:
Professor Ingo Ebersberger
Institute of Cell Biology and Neuroscience
51猎奇 Frankfurt
Tel.: +49 69 798 42112
ebersberger@bio.uni-frankfurt.de
Homepage:
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.