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.
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).
has been the bane of many drug researchers.
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)
Innovative Medicines Initiative (IMI) on Europa
Headlines article on XDR-TB (28 September 06)