A new target identified to combat a dangerous Melioidosis infection

by Ronja Münch, Leibniz-Institut für Naturstoff-Forschung und Infektionsbiologie – Hans-Knöll-Institut (Leibniz-HKI)

The active site of the enzyme BurG, which produces a reactive compound that plays an important role in melioidosis. Credit: Michael Groll/Felix Trottmann

Researchers at the Leibniz Institute for Genetic Research and Infection Biology – Hans Knöll Institute (Leibniz-HKI) in Jena, Germany have discovered an enzyme that holds the promise of a new therapeutic target to fight the dangerous disease melioidosis. It helps the pathogenic bacteria Burkholderia pseudomallei build a toxin that is important in the infection process. The results are 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 Department of Biomolecular Chemistry at Leibniz-HKI and professor of biochemistry at the Friedrich Schiller University in Jena, explains. “And also vaccine it often drags on for months and is not always successful because common drugs do not work well against these diseases.

So his research team wanted to understand the bacteria infection ways and came across a new possible place to fight the disease. “We found someone enzyme which links the molecular mechanisms at the center of infection,” said Felix Trottmann, first author of the study.

The enzyme BurG was discovered to form the cyclopropanol ring, a highly reactive chemical functional group, from the primary molecule. In previous research, Trottmann was able to show that this process also produces some harmful bacteria in the genus Burkholderia and apparently has an important role in infection. If before biosynthetic pathway because this gene kills by mutation, the virus is not very dangerous.

The research team also revealed the 3D structure of the enzyme in collaboration with TU Munich. “In the next step, we can now try to create active compounds that inhibit the enzyme and thus make the bacteria inactive,” Trottmann said. According to current knowledge, the enzyme is found only in bacteria and not in humans. “So the hope is to be able to prevent bacteria specifically,” Hertweck said. The immune system can easily deal with them.

To understand plant biosynthesis genetic structure In the middle of the infection, the researchers looked at the collection of genes that contain the DNA instructions to make it. They conducted laboratory tests using Burkholderia thailandensis, which is similar to Burkholderia pseudomallei but safer to work with.

Melioidosis is more common in Southeast Asia and Australia. However, experts have warned that the disease may spread further. For example, the US Centers for Disease Control and Prevention (CDC) was able to trace the cause of four outbreaks of melioidosis last year, two of which were fatal, to deodorant sprays. Close by related species, B. mallei, which also produces the cyclopropanol ring, was used as a biological weapon in World War I and II. And B. pseudomallei has also been researched in other countries.

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Additional information:
Felix Trottmann et al, Pathogenic bacteria re-engineered the central enzyme to construct a cyclopropanol warhead, Nature Chemistry (2022). DOI: 10.1038/s41557-022-01005-z

Provided by the Leibniz-Institut für Naturstoff-Forschung und Infektionsbiologie – Hans-Knöll-Institut (Leibniz-HKI).

hintA New Target Discovered to Combat Dangerous Melioidosis Infection (2022, August 1) Retrieved August 1, 2022 from .html

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