University of Warwick

Novel key to unlock hundreds of new antibiotics identified

Chemists at the University of Warwick and the John Innes Centre have uncovered a new signalling molecule, which can unlock hundreds of new antibiotics from the DNA of the Streptomyces family of bacteria.

Washington, Oct 30 : Chemists at the University of Warwick and the John Innes Centre have uncovered a new signalling molecule, which can unlock hundreds of new antibiotics from the DNA of the Streptomyces family of bacteria.

Researchers have already developed methods to find and exploit new pathways for antibiotic production in the genome of the Streptomyces family and many Streptomyces bacteria are being used industrially to produce current antibiotics.It has long been believed that the relatively unstable butyrolactone compounds represented by "A-factor" were the only real signal for stimulating such pathways of possible antibiotic production

However, the researchers have now found a much more stable group of compounds that could produce at least one new antibiotic compound from up to 50pct of the 1000 or so known Streptomyces family of bacteria.

Usually, colonies of bacteria such as Streptomyces naturally make antibiotics as a defence mechanism when under stress and are thus more susceptible to attack from other bacteria. But the colonies need to produce a compound to spread a signal across the colony to start producing their natural antibiotic weapons.

The researchers used the University of Warwick's 700 MHz NMR machine to get a close look at just micrograms of 5 new possible signalling compounds identified as 2-alkyl-4-hydroxymethylfuran-3-carboxylic acids (or AHFCAs).

Led by Dr Christophe Corre, and Professor Greg Challis from the University of Warwick's Department of Chemistry, researchers could combine their new insight into these compounds with the relatively new full genetic sequences now available of some Streptomyces bacteria.

The researchers were convinced that the AHFCA group of compounds could play a role in stimulating the production of known and novel antibiotics.

On adding AHFCAs to Streptomyces coelicolor W81, they were proved correct as it stimulated the production of methylenomycin antibiotics.

The researchers speculated that novel pathways for antibiotic production are also under the control of AHFCAs. The AHFCAs should be relatively easy to make in significant quantity in a lab and could be used as a new tool for discovery of antibiotics and develop a novel approach for drug discovery..

Christophe Corre, from the University of Warwick's Department of Chemistry said: "Early results also suggest that this approach could switch on novel antibiotic production pathways in up to 50% of Streptomyces bacteria. With thousands of known members of the Streptomyces family that could mean that AHFCAs could unlock hundreds of new antibiotics to replenish our dwindling arsenal of effective antibiotic drugs."

ANI