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Updated: Jan 11, 2026
Total Protein Extraction and 2-D Gel Electrophoresis Methods for Burkholderia Species
Published on: October 15, 2013
Inactivation of the Burkholderia Toxin Malleicyprol by Enzymatic Cyclopropanol Ring Opening
Jonas Fiedler1, Ingrid Richter1,2, Katharina Dornblut1
1Department of Biomolecular Chemistry, Leibniz Institute for Natural Product Research and Infection Biology (HKI), Beutenbergstraße 11a, 07745, Jena, Germany.
Abstract:
Pathogenic bacteria of the Burkholderia pseudomallei group cause life-threatening infections in humans and animals. Their virulence factors include malleicyprols bearing a reactive cyclopropanol moiety essential for toxicity. Inactivating this reactive motif, therefore, is a promising way to neutralize these toxins. Here, we identify a heme-dependent oxidoreductase (BurK) that cleaves the cyclopropanol warhead. Mutational analyses and in vivo radical capturing show that BurK catalyzes a radical ring opening to yield a propanone fragment. Characterizing BurK orthologs across various bacterial phyla suggests broader ecological roles of these unusual enzymes. Using a nematode model, we demonstrate that BurK-producing helper bacteria neutralize malleicyprols, significantly reducing toxicity and enhancing host survival. In addition to uncovering a novel biocatalyst, this work lays the foundation for antivirulence approaches using therapeutic microbes against antibiotic-resistant pathogens.
Insights
Scientists discovered a novel enzyme, BurK, that neutralizes toxic bacterial compounds called malleicyprols. This finding offers a new strategy for developing antivirulence therapies against dangerous, antibiotic-resistant pathogens.
Area of Science:
- Microbiology
- Biochemistry
- Pathogen Research
Background:
- The Burkholderia pseudomallei group causes severe infections.
- Malleicyprols, with a reactive cyclopropanol group, are key virulence factors.
Purpose of the Study:
- Identify mechanisms to neutralize malleicyprol toxicity.
- Discover novel biocatalysts for antivirulence strategies.
Main Methods:
- Enzyme identification and characterization (BurK).
- Mutational analyses and in vivo radical capturing.
- Nematode infection models to assess toxicity reduction.
Main Results:
- A heme-dependent oxidoreductase (BurK) was identified that cleaves the malleicyprol cyclopropanol moiety.
- BurK catalyzes a radical ring opening, yielding a propanone fragment.
- BurK-producing bacteria significantly reduce malleicyprol toxicity and enhance host survival in a nematode model.
Conclusions:
- BurK is a novel biocatalyst that inactivates bacterial toxins.
- This discovery supports the development of antivirulence therapies using microbes against antibiotic-resistant bacteria.
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