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01.04.2019

Bacteria produce antibiotics cocktail

Frankfurt-based biotechnologists have discovered how bacteria build up their arsenal of antibiotic substances.

Agar plate with phenazine producer Xenorhabdus szentirmaii. The metallic glow comes from the phenazine derivative iodinine.
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Helge Bode

The fight against bacterial infectious diseases is an urgent problem worldwide. Due to the increase in antibiotic-resistant pathogens, many common preparations have lost their effect. According to the World Health Organization (WHO), antibiotic resistance is one of the "greatest threats to human health". When looking for alternatives to common active substances, the defence arsenal of bacteria is a valuable source. In order to defend themselves against competing microorganisms, bacteria use a variety of strategies. Biotechnologists at the Goethe University in Frankfurt am Main have discovered a new mechanism for the formation of antibiotic active substances in the bacterium Xenorhabdus szentirmaii. They present their discovery in the journal "Nature Chemical Biology".

A mix of active compounds against competitors

The biotechnologists have investigated the class of phenazines in more detail. Phenazines are widespread, chemically very diverse bacterial natural products with varying biological functions. Some of these substances have an antibiotic or cell-damaging effect. Bacteria probably use a cocktail of phenazines to compete against rival bacteria and fungi in their specific ecosystems.

The various phenazine derivatives of the bacterial drug cocktail are biochemically derived from simple basic structures. Enzymes can drastically modify the basic structures in the periphery. A large number of possible phenazine derivatives are conceivable, some of which have also been found in different bacteria. These bacteria basically use similar principles to industrial pharmaceutical research when they generate new derivatives on the basis of the same basic structures.

Broad biological activity through diversity

The Molecular Biotechnology research group led by Professor Helge Bode has now succeeded in identifying new mechanisms that allow the bacteria to modify these simple basic structures, resulting in derivatives that act on both Gram-positive and Gram-negative bacteria, as well as on cells of higher organisms. With the strategy of producing a mix of derivatives, the bacteria are well equipped to counteract unknown competitors, as the cocktail of derivatives exhibits a wide range of biological activity.

The microbes therefore proceed in a similar way to pharmaceutical research in order to expand their own antibiotic arsenal. “It would now be fascinating to find out how bacteria actually recognise which derivatives are required at a given time,” states Helge Bode. “Either they produce only those derivatives that are actually required, or the bacteria keep an arsenal of derivatives so that they are prepared for any situation.” First results on the underlying regulation mechanisms that could also be used for biotechnical applications appear promising.

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