Preclinical antibiotic captured at work

A new preclinical antibiotic that is being developed by GlaxoSmithKline Plc has been shown in an image fighting bacteria that are resistant to conventional antibiotics.

The image, which was produced by x-ray crystallography, shows the new compound, GSK 299423, attaching to topoisomerase, an enzyme that controls changes in the structure of DNA in bacteria. Inhibitors of topoisomerase have been successfully used as antibiotics for decades, but bacteria increasingly are developing resistance to this class of drugs.

Now, GSK and its collaborator, the Wellcome Trust, have released an image which shows the preclinical compound attaching to topoisomerase in a different place than a conventional antibiotic would. Although still in very early development, the data has raised expectations that a new class of broad-spectrum antibiotics might be developed to block topoisomerase in bacteria resistant to current treatments. Stopping the enzyme prevents the bacteria from reproducing.

The investigational compound is being developed in a collaboration that includes GSK, the Wellcome Trust and the Defense Threat Reduction Agency, an agency of the US Department of Defense. The image, and a report on the research, were published online in the journal Nature on 4 August 2010. The image can also be viewed with this story, courtesy of GSK.

The compound is being developed to treat antibiotic-resistant strains of bacteria such as Staphylococus aureus, including methicillin resistant S. aureus as well as against Gram-negative bacteria. Many current antibiotics have difficulty attacking Gram-negative bacteria because these bacteria have a tough outer membrane surrounding the bacterial cell wall protecting them from invasion.

“This is an important step forward in the race against antibiotic resistance,” Ted Bianco of the Wellcome Trust, said in a prepared statement.

“By solving the new structure of this important bacterial enzyme, and understanding how these drugs work, the team has opened the door for targeted drug design of new antibiotics, which are urgently needed,” he said.

Copyright 2010 Evernow Publishing Ltd

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