Australian chemists have developed a potential new antibiotic that could help in the battle against antibiotic resistant bacteria, including the methicillin-resistant Staphylococcus aureus.

“Existing antibiotics target the bacterial cell membranes but this potential new antibiotic operates in a completely different way,” explained Prof Andrew Abell from the University of Adelaide’s School of Chemistry and Physics, who is a senior author of the paper published in the journal Chemical Science.

“The compound, although at a very early stage of development – it has not yet been tested on an animal model – has the potential to become the first of a new class of antibiotics.”

The compound is a protein inhibitor that binds to an enzyme called biotin protein ligase, stopping its action and interrupting the life cycle of the bacteria.

“Bacteria quickly build resistance against the known classes of antibiotics and this is causing a significant global health problem,” Prof Abell said. “Preliminary results show that this new class of compound may be effective against a wide range of bacterial diseases, including tuberculosis which has developed a strain resistant to all known antibiotics.”

The scientists used a novel approach called ‘in situ click chemistry’ to develop the new protein inhibitor. “A selection of small molecules is presented to the bacteria in a way so that the target protein enzyme itself builds the inhibiting compound and also binds with it.”

“In a sense the bacteria unwittingly chooses a compound that will stop its growth and assembles it – like building a weapon and using it against itself. We’ve gone a step further to specifically engineer the enzyme so that it builds the best and most potent weapon.”

“Our results are promising. We’ve made the compounds; we know they bind and inhibit this enzyme and we’ve shown they stop the growth of a range of bacteria in the laboratory. The next critical step will be investigating their efficacy in an animal model,” Prof Abell concluded.

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Bibliographic information: William Tieu et al. Optimising in situ click chemistry: the screening and identification of biotin protein ligase inhibitors. Chem. Sci., published online June 19, 2013; doi: 10.1039/C3SC51127H