Press releases – October 2022

Using bacteria of the Bartonella henselae species, researchers from Goethe University, 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. https://journals.asm.org/doi/10.1128/spectrum.02117-22

Background: How bacteria adhere to cells: Basis for the development of a new class of antibiotics (22 June 2022) https://www.goethe-university-frankfurt.de/74958144?search=kempf

Picture download:
https://www.kgu.de/fileadmin/redakteure/Presse/Bilder_Pressmitteilungen/2022/Bartonella_henselae.jpg

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: https://www.mdpi.com/2075-4418/11/7/1259

Further information:
Professor Volkhard A. J. Kempf
Director of the Institute of Medical Microbiology and Hospital Hygiene
University Hospital Frankfurt
Goethe University Frankfurt
Phone: +49 (0)69 6301–5019
volkhard.kempf@kgu.de
Website: https://www.kgu.de/einrichtungen/institute/zentrum-der-hygiene/medizinische-mikrobiologie-und-krankenhaushygiene

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 Goethe University 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 Goethe University 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 Goethe University 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) https://doi.org/10.1016/j.jpain.2022.07.005

Picture download:

https://www.uni-frankfurt.de/126745085

Caption: People who sit a lot and do not exercise often develop back pain. Credits: Markus Bernards for Goethe University Frankfurt

Further information:

Dr. Johannes Fleckenstein
Sports Medicine and Exercise Physiology
Institute of Sports Sciences
Goethe University 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.