idw – Informationsdienst Wissenschaft

Nachrichten, Termine, Experten

Grafik: idw-Logo
Science Video Project
idw-Abo

idw-News App:

AppStore

Google Play Store



Instance:
Share on: 
08/01/2022 10:40

Melioidosis: A new target identified to combat a dangerous bacterial infection

Ronja Münch Pressestelle
Leibniz-Institut für Naturstoff-Forschung und Infektionsbiologie - Hans-Knöll-Institut (Leibniz-HKI)

    Researchers at the Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute (Leibniz-HKI) in Jena, Germany have identified an enzyme that is a promising new therapeutic target to combat the dangerous bacterial disease melioidosis. It helps the pathogenic bacterium Burkholderia pseudomallei construct a toxic molecule that is critical in the infection process. The results were published in Nature Chemistry.

    Melioidosis is a life-threatening disease caused by the bacterium Burkholderia pseudomallei. "Without treatment, the disease is usually fatal," Christian Hertweck, head of the Biomolecular Chemistry Department at Leibniz-HKI and professor of natural product chemistry at Friedrich Schiller University in Jena, explains. "And even antibiotic treatment often drags on for many months and is not always successful because common drugs do not work well against these pathogens."

    His research group therefore wanted to understand the bacterium's infection mechanisms and has come across a possible new starting point for combating the disease. "We have found an enzyme that synthesises a molecular structure central to the infection," explains Felix Trottmann, first author of the study.

    The discovered enzyme BurG forms a cyclopropanol ring, a highly reactive chemical functional group, from a precursor molecule. In previous studies, Trottmann was able to demonstrate that this structure is also produced by other pathogenic bacteria in the genus Burkholderia and apparently has an important role in infection. If the biosynthetic pathway for this molecule is switched off by mutations, the bacteria are far less dangerous.

    The research team has also elucidated the 3D structure of the enzyme in cooperation with TU Munich. "In a next step, we can now try to design active compounds that inhibit the enzyme and thus make the bacteria less virulent," Trottmann explains. According to current knowledge, the enzyme is only found in bacteria and not in humans. "The hope is therefore to be able to specifically inhibit the bacteria," says Hertweck. The immune system could then deal with them more easily.

    To understand the biosynthesis of the molecular structure central to infection, the researchers investigated the gene cluster that contains the DNA instructions for making it. They conducted the laboratory experiments using Burkholderia thailandensis, which is very similar to Burkholderia pseudomallei but is much safer to work with.

    Melioidosis mainly occurs in Southeast Asia and Australia. However, experts warn that the disease could spread further. For example, the US Centers for Disease Control and Prevention (CDC) were able to trace the cause of four cases of melioidosis last year, two of which were fatal, to an aromatherapy spray. A closely related species, B. mallei, which also produces the cyclopropanol ring, was used as a biological weapon in both World War I and World War II. And B. pseudomallei was also researched as such in some countries.

    The study was supported by the German Research Foundation within the framework of the Collaborative Research Centres 1127 (ChemBioSys) and 1309. In addition, the researchers were supported by the European Regional Development Fund, the Daimler and Benz Foundation and the Chemical Industry Fund. Christian Hertweck used funds from the Gottfried Wilhelm Leibniz Prize for the project, which he was awarded in 2015.


    Contact for scientific information:

    Prof. Dr. Christian Hertweck
    Biomolecular Chemistry
    Leibniz-Institute for Natural Product Research and Infection Biology
    - Hans Knöll Insitute -
    christian.hertweck@leibniz-hki.de


    Original publication:

    Trottmann F, Ishida K, Ishida-Ito M, Kries H, Groll M, Hertweck C (2022). Pathogenic bacteria remodel central metabolic enzyme to build a cyclopropanol warhead. Nature Chemistry. https://www.doi.org/10.1038/s41557-022-01005-z


    Images

    Active centre of the enzyme BurG, which forms a highly reactive chemical compound that plays a crucial role in melioidosis.
    Active centre of the enzyme BurG, which forms a highly reactive chemical compound that plays a cruci ...
    Michael Groll/Felix Trottmann


    Criteria of this press release:
    Journalists
    Biology, Medicine
    transregional, national
    Research results, Scientific Publications
    English


     

    Active centre of the enzyme BurG, which forms a highly reactive chemical compound that plays a crucial role in melioidosis.


    For download

    x

    Help

    Search / advanced search of the idw archives
    Combination of search terms

    You can combine search terms with and, or and/or not, e.g. Philo not logy.

    Brackets

    You can use brackets to separate combinations from each other, e.g. (Philo not logy) or (Psycho and logy).

    Phrases

    Coherent groups of words will be located as complete phrases if you put them into quotation marks, e.g. “Federal Republic of Germany”.

    Selection criteria

    You can also use the advanced search without entering search terms. It will then follow the criteria you have selected (e.g. country or subject area).

    If you have not selected any criteria in a given category, the entire category will be searched (e.g. all subject areas or all countries).