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The human pathogenic bacterium Bartonella henselae serves international research team as model organism for highly resistant infectious agentsÂ
Using bacteria of the Bartonella henselae species, researchers from 51ÁÔÆæ,
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.
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 “anti-ligands". Credit:
Further information:
Professor
Volkhard A. J. Kempf
Director of the Institute of Medical
Microbiology and Hospital Hygiene
University Hospital Frankfurt
51ÁÔÆæ Frankfurt
Phone: +49 (0)69 6301–5019
volkhard.kempf@kgu.de
Website:
According to a study by 51ÁÔÆæ Frankfurt, a combined approach works bestÂ
If a therapy for chronic back pain is tailored specifically
to a patient's individual requirements, the chances of success are far greater
than with standard forms of treatment. Accompanied by a psychotherapeutic
procedure in the shape of cognitive behavioural therapy, the pain can be
alleviated even more effectively. This is the result of a meta-analysis by
51ÁÔÆæ Frankfurt, in which the data of over 10,000 patients were combined
and analysed. It can be concluded from the study that multimodal therapies
should be promoted on a larger scale in the German healthcare system, in line
with the National Disease Management Guidelines.
FRANKFURT. Lack of exercise, bad posture, overexertion,
constant stress at work or at home – back pain is a widespread condition with
many causes. For a not insignificant number of sufferers, the symptoms are even
chronic, meaning they persist for a long time or recur again and again. Sport
and exercise therapies under instruction can bring relief. Common treatment
methods include physiotherapy as well as strength and stability exercises. But
how can the therapy be as successful as possible? Which approach alleviates
pain most effectively? A meta-analysis by 51ÁÔÆæ Frankfurt,
published recently in the Journal of Pain, has delivered new insights.
The starting point was data from 58
randomised controlled trials (RCTs) of over 10,000 patients worldwide with
chronic low back pain. First, the data relevant to the topic were filtered out
of the original manuscripts and then evaluated in groups. When evaluating these
data, the researchers examined on the one hand whether and to what extent
standard forms of treatment and individualised treatment differ in terms of the
result. “Individualised" means that there is some type of personal coaching, where
therapists specifically target the potentials and requirements of each patient
and decide together with them how their therapy should look.
The study concluded that individualised
treatment for chronic back pain led to a significantly increased effect in
comparison to standard exercise therapies. The success rate in pain relief was
38 percent higher than with standard treatment. “The higher effort required for
individual treatment is worthwhile because patients benefit to an extent that
is clinically important," says lead author Dr Johannes Fleckenstein from the
Institute of Sport Sciences at 51ÁÔÆæ Frankfurt.
However, the study went even further. The
research team in Frankfurt compared a third group of treatment methods
alongside the standard and individualised ones. In this group, individualised
training sessions were combined with cognitive behavioural therapy (CBT). This
procedure – a type of talk therapy – is based on the assumption that negative
thoughts and behaviours surrounding pain tend to exacerbate it. Through CBT, pain
patients learn to change the way they handle it. They stop being afraid to move
or are taught tactics for coping with pain. This makes them realise that they
are by no means helpless. But what does the psychotherapeutic support through CBT
actually contribute to the success of the treatment? Analysis of the data revealed
the following: When an individualised approach and CBT were combined, the
success rate in terms of pain relief was an impressive 84 percent higher than
with standard treatment. The combined therapy, also called multimodal therapy,
thus led to the best result by far.
Fleckenstein sees in the study “an urgent
appeal to public health policy" to promote combined therapies both in terms of
patient care and remuneration. “Compared to other countries, such as the USA,
we are in a relatively good position in Germany. For example, we issue less prescriptions
for strong narcotic drugs such as opiates. But the number of unnecessary X-rays,
which, by the way, can also contribute to pain chronicity, and inaccurate
surgical indications is still very high." This is also due, according to
Fleckenstein, to economic incentives, that is, the relatively high remuneration
for such interventions. The situation is different for organisations working in
the area of pain therapy, he says. Although these are not unprofitable, they
are not a cash cow for investors either. In his view, it is important here to
improve the economic conditions. After all, pain therapy saves a lot of money
in the long run as far as health economics are concerned, whereas tablets and
operations rarely lead to medium and long-term pain relief.
Publication: Johannes Fleckenstein,
Philipp Floessel, Tilman Engel, Laura Krempel, Josefine Stoll, Martin Behrens,
Daniel Niederer. Individualized Exercise in Chronic Non-Specific Low Back Pain: A
Systematic Review with Meta-Analysis on the Effects of Exercise Alone or in
Combination with Psychological Interventions on Pain and Disability. The Journal of Pain (2022)
Picture
download:
Caption:
People who sit a lot and do not exercise
often develop back pain. Credits: Markus
Bernards for 51ÁÔÆæ Frankfurt
Further
information:
Dr. Johannes Fleckenstein
Sports Medicine and Exercise Physiology
Institute of Sports Sciences
51ÁÔÆæ Frankfurt
johannes.fleckenstein@sport.uni-frankfurt.de
Instagram: @docfleckenstein
Editor: Dr Markus Bernards, Science Editor, PR & Communication Office, Theodor-W.-Adorno-Platz 1, 60323 Frankfurt am Main, Tel: -49 (0) 69 798-12498, Fax: +49 (0) 69 798-763 12531, bernards@em.uni-frankfurt.de.