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Headlines Published on 15 December 2006

Title EU-funded consortium making strides in fight to exterminate ‘superbugs’

As antibiotics have solved some of the major medical problems in recent history, so too have they contributed to the rise of a whole new set of challenges - antibiotic resistant bacteria. Studies show that improper or excessive doses of antibiotics have augmented the number of ‘superbugs’, or drug resistant organisms. Some well known cases include MRSA, common in hospitals and first detected in the UK in the 60s, and extensively drug-resistant tuberculosis (XDR-TB). The European Union has taken notice of the problem and funded the CombiGyrase consortium to combat the rising tide of such bacteria.

MRSA has been the bane of many drug researchers. © Matt+
MRSA has been the bane of many drug researchers.
CombiGyrase has made important strides in identifying strategies used to fight drug resistant pathogens. One challenge is to target a portion of the bacterium that is not found naturally in humans and design methods to attack that characteristic. That way experts can develop drugs to eliminate the harmful organisms without damaging normal healthy tissue. CombiGyrase has been successful in establishing such structures found in bacteria. They have identified the bacterial enzyme DNA gyrase as the proper candidate to help bring down resistant superbugs. DNA gyrase is not found in humans and has been the focus of other efficacious drug solutions in the past, such as the anti-anthrax drug Cipro (though Cipro has since spawned its own generation of resistant organisms).

CombiGyrase began their research by looking at known DNA gyrase inhibitors called aminocoumarins. Consortium experts wondered if aminocoumarins (such as novobiocin and clorobiocin), which in spite of their potency had performed poorly in clinical tests, could be redesigned to researchers’ advantage.

Aminocoumarins are produced naturally by other bacteria which use them to kill off rivals, and researchers have been able to isolate the genes that produce them to potentially generate derivatives. The principle output from CombiGyrase has been large numbers of totally new aminocoumarin compounds, called novclobiocins, which have been tested for their ability to target DNA gyrase. Their work has produced compounds which exhibit greatly improved properties over the original raw materials.

Perhaps the most noteworthy innovation to come from CombiGyrase has been the development of Simocyclinone, a type of aminocoumarin that operates under an entirely new mode of behaviour. The hope is that this discovery can be used to engineer completely new drugs to fight superbugs.

CombiGyrase is a European consortium comprised of seven labs from five countries: Germany, Switzerland, Italy, Spain and the UK. It is headed by Prof. Lutz Heide from the University of Tübingen (Germany). The group began work three years ago and is funded as a Specific Targeted Research Project (STREP) under FP6.

More information:

  • CombiGyrase homepage
  • Innovative Medicines Initiative (IMI) on Europa
  • Headlines article on XDR-TB (28 September 06)

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