New finding could lead to development of hundreds of new antibiotics
EU-funded scientists have discovered a new molecule in Streptomyces bacteria that could be exploited to make the bacteria produce hundreds of novel antibiotics. The work, which is published online by the Proceedings of the National Academy of Sciences (PNAS), was partly supported by the EU-funded ACTINOGEN (Integrating genomics-based applications to exploit actinomycetes as a resource for new antibiotics) project.
When colonies of bacteria such as Streptomyces are under stress and so more vulnerable to attack from other bacteria, a signal is sent out across the colony that stimulates the bacteria to make antibiotics as a defence mechanism.
Drug manufacturers have exploited this characteristic of the Streptomyces bacteria for some time, using certain strains to produce antibiotics on an industrial scale. In most of these cases, the compounds used to trigger the bacterial defence mechanism are relatively unstable.
In this latest piece of research, scientists from the University of Warwick and the John Innes Centre in the UK succeeded in identifying a much more stable group of compounds called 2-alkyl-4-hydroxymethylfuran-3-carboxylic acids (AHFCAs) that could have the potential to stimulate different pathways of antibiotic production in the bacteria. This could eventually lead to the development of many novel antibiotics.
Normally the amounts of these defence-mechanism-triggering compounds produced by the bacteria are too small for chemists to analyse easily. In this study, the scientists used the University of Warwick's 700 MHz NMR (Nuclear Magnetic Resonance) machine to identify the AHFCAs on the basis of just a few micrograms of material.
The chemists combined their newfound knowledge with information on the genetic sequences of some Streptomyces bacteria to show that the AHFCA group of compounds could potentially be used to stimulate the production of both known and new antibiotics. Their hypothesis was confirmed when they added the AHFCAs to colonies of the W81 strain of Streptomyces coelicolor; the bacteria produced methylenomycin antibiotics.
Although methylenomycins are a familiar type of antibiotic, the researchers believe that the AHFCAs could also control the production of novel types of antibiotic.
"Early results also suggest that this approach could switch on novel antibiotic production pathways in up to 50% of Streptomyces bacteria," said Dr Christophe Corre of the University of Warwick, the lead author of the paper. "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."
The researchers are now on the lookout for funding to explore the properties of AHFCAs further.
The ACTINOGEN project received approximately EUR 9.4 million in EU funding through the 'Life sciences, genomics and biotechnology for health' Thematic area of the Sixth Framework Programme (FP6).
For more information, please visit:
Proceedings of the National Academy of Sciences (PNAS), http://www.pnas.org
University of Warwick, http://www.warwick.ac.uk
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