06-Apr-2022 - Johann Wolfgang Goethe-Universität Frankfurt (Main)

Achilles’ heel of dangerous hospital pathogen discovered

Structural analysis revealed weak spots

A team from Research Unit 2251 of the German Research Foundation led by Goethe University has shed light on the structure of an enzyme important in the metabolism of the pathogenic bacterium Acinetobacter baumannii. The enzyme “MtlD” is critical for the bacterium’s synthesis of the sugar alcohol mannitol, with which it protects itself against water loss and desiccation in dry or salty environments such as blood or urine. Structural analysis has revealed weak spots where it might be possible to inhibit the enzyme and thus attack the pathogen.

Each year, over 670,000 people in Europe fall ill through pathogenic bacteria that are resistant to antibiotics, and 33,000 die of the diseases they cause. In 2017, the WHO named antibiotic resistance as one of the greatest threats to health worldwide. Especially feared are pathogens that are resistant to several antibiotics. Among them, Acinetobacter baumannii stands out, a bacterium with an extraordinarily pronounced ability to develop multiresistance and, as a “hospital superbug”, dangerous above all for immunosuppressed patients. Acinetobacter baumannii is highly resilient because it can remain infectious for a long time even in a dry environment and thus endure on the keyboards of medical devices or on ward telephones and lamps. This property also helps the microbe to survive on dry human skin or in body fluids such as blood and urine, which contain relatively high concentrations of salts and other solutes.

The team from Research Unit 2251 of the German Research Foundation led by Goethe University has now shed light on a central mechanism via which Acinetobacter baumannii settles in such an adverse environment: like many bacteria as well as plants or fungi, Acinetobacter baumannii is able to synthesize the sugar alcohol mannitol, a substance excellent at binding water. In this way, Acinetobacter baumannii prevents desiccation.

Almost unique, however, is the way that Acinetobacter baumannii synthesizes mannitol: instead of two enzyme complexes as are common in most organisms, the two last steps in mannitol synthesis are catalysed by just one. A team of researchers led by Professor Beate Averhoff and Professor Volker Müller already discovered this “MtlD” enzyme with two catalytic activities back in 2018. The team headed by Professor Klaas Martinus Pos, who is also a member of the Research Unit, has now succeeded in shedding light on the enzyme’s spatial structure.

e explains: “We’ve discovered that the enzyme is usually present in the form of free monomers. Although these have the necessary catalytic activities, they are inactive. Only a dry or salty environment triggers what is known as ‘osmotic stress’ in the bacterium, after which the monomers aggregate as dimers. Only then does the enzyme become active and synthesize mannitol.” The researchers have also identified which parts in the structure are particularly important for the enzyme’s catalytic functions and for dimer formation.

Professor Volker Müller, spokesperson for Research Unit 2251, is convinced: “Our work constitutes an important new approach for fighting this hospital pathogen since we’ve identified a biochemically sensitive point in the pathogen’s metabolism. In the future, this could be the starting point for customized substances to inhibit the enzyme.”

Facts, background information, dossiers

  • enzymes
  • Acinetobacter baumannii
  • bacteria
  • structural analysis
  • antibiotic resistance

More about Uni Frankfurt am Main

  • News

    How do killer T cells know where danger is coming from?

    How do killer T cells recognise cells in the body that have been infected by viruses? Matter foreign to the body is presented on the surface of these cells as antigens that act as a kind of road sign. A network of accessory proteins – the chaperones – ensure that this sign retains its stabi ... more

    Laboratory study: effect of antibodies against omicron variants BA.1 and BA.2 wears off quickly

    The omicron variants BA.1 and BA.2 of the SARS-CoV-2 virus, which are dominant from about December to April, can undermine the protection against infection offered by vaccinations or survived infections after only three months. This is shown by a study from Frankfurt under the leadership of ... more

    How bacteria adhere to cells: Basis for the development of a new class of antibiotics

    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 t ... more

  • q&more articles

    From feast to famine and back – no problem for bacteria

    Bacteria are true survivors. In the course of evolution, they have developed numerous strategies to adapt to rapidly changing, uncertain environmental conditions. Their metabolism is much more sophisticated than that of human beings. Within minutes they can regulate their gene expression an ... more

    Why biosimilars and not biogenerics?

    Medicines produced using genetic techniques have existed since 2006, called “similar biological medicinal products” or “biosimilars”. Until a year ago, this was a fairly low-profile group, even in expert circles. This has all changed now, however, with the recent licensing of the first bios ... more

    Paradigm shift

    What would medicine be without drugs? But are these drugs being used optimally today? Not at all, as we now know thanks to the findings of molecular medicine. Because for the use of these drugs, it is important to observe two aspects: the disease and the patient. Only slowly is it becom ... more

  • Authors

    Prof. Dr. Claudia Büchel

    Claudia Büchel, born in 1962, studied biology at the University of Mainz, where she also received her doctorate and, in 2001, the qualification to teach plant physiology. After a postdoctoral research period at the Biological Research Centre, Szeged, she worked for four years as a research ... more

    Prof. Dr. Jörg Soppa

    Jörg Soppa, born in 1958, studied biochemistry in Tübingen and then went on to do his doctorate at the Max Planck Institute of Biochemistry in Martinsried near Munich. In 1990 he established his own research group there and held courses at the Institute of Genetics and Microbiology of Munic ... more

    Prof. Dr. Heinfried H. Radeke

    Heinfried H. Radeke studied medicine at the Hannover Medical School (MHH) and received his medical license in 1985. His Ph.D. thesis was recognized as the best research dissertation of 1986. After two years as an assistant physician at the Göttingen University Hospital, he began his career ... more

q&more – the networking platform for quality excellence in lab and process

The q&more concept is to increase the visibility of recent research and innovative solutions, and support the exchange of knowledge. In the broad spectrum of subjects covered, the focus is on achieving maximum quality in highly innovative sectors. As a modern knowledge platform, q&more offers market participants one-of-a-kind networking opportunities. Cutting-edge research is presented by authors of international repute. Attractively presented in a high-quality context, and published in German and English, the original articles introduce new concepts and highlight unconventional solution strategies.

> more about q&more

q&more is supported by: