CARDIFF U. (UK) — A bacterium that can cause severe lung infection in people with cystic fibrosis is effective in fighting a variety of drug-resistant microbes, including MRSA.
Using forensic fingerprinting tests to genetically identify Burkholderia, Eshwar Mahenthiralingam of Cardiff University screened it for antibiotics active against other bacteria, particularly drugs with the potential to kill other bacteria that infect cystic fibrosis patients.
Mahenthiralingam’s team discovered that around one quarter of Burkholderia bacteria have extremely strong antibiotic activity on multidrug-resistant pathogens such as MRSA. One particular strain, Burkholderia ambifaria, was found to produce two very potent antibiotics active on resistant bacteria, in particular Acinetobacter baumanii.
The chemical structures of the antibiotics, called enacyloxins, were determined by Gregory Challis and Lijiang Song at the University of Warwick, demonstrating that they belong to one of the most successful families of natural product drugs, the polyketides.
Other examples of polyketides include erythromycin, which is used to cure many bacterial infections, and doxorubin, used as an anti-cancer drug. “The combination of enzymes used by Burkholderia to make the enacyloxins is very unusual, Challis says. “Our insights into this process should allow us to use cutting edge synthetic biology techniques to produce novel enacyloxin analogs with improved pharmaceutical properties.”
The research is published in the journal Chemistry and Biology.
“Burkholderia are soil bacteria like Streptomyces, which are the source of most of our current antibiotics,” says Mahenthiralingam. ”
Our research therefore offers real hope of a completely new source for the identification and engineering of highly potent antibiotics. With antibiotic resistant bacteria causing great suffering around the world, these new sources are urgently needed.”
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