University of Adelaide research has produced a potential new antibiotic² which could help in the battle against bacterial³ resistance to antibiotics⁴. The potential new antibiotic targets a bacterial enzyme⁵ critical to metabolic⁶ processes.

 

The compound is a protein inhibitor（抑制剂） which binds⁹ to the enzyme (called biotin生物素 protein ligase), stopping its action and interrupting the life cycle of the bacteria.

 

"Existing antibiotics target the bacterial cell membranes¹⁰ but this potential new antibiotic operates in a completely different way," says Professor Andrew Abell, project leader and Acting¹¹ Head of the University's School of Chemistry and Physics.

 

Professor Abell says 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.

 

"Bacteria quickly build resistance against the known classes of antibiotics and this is causing a significant global health problem," he says. "Preliminary results show that this new class of compound may be effective against a wide range of bacterial diseases, including tuberculosis¹² which has developed a strain resistant¹³ to all known antibiotics."

 

Developing the new protein inhibitor involved a novel approach called 'in situ click chemistry'. A selection of small molecules¹⁴, or 'precursor¹⁵ fragments', are presented to the bacteria in a way so that the target protein enzyme itself builds the inhibiting¹⁶ compound and also binds with it.

 

"In a sense the bacteria unwittingly（不知不觉地） chooses a compound that will stop its growth and assembles it -- like building a weapon and using it against itself," says Professor Abell. "We've gone a step further to specifically engineer the enzyme so that it builds the best and most potent¹ weapon."

 

"Our results are promising¹⁷. We've made the compounds; we know they bind⁸ and inhibit⁷ 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."

 

"Thanks to this new approach what might have taken a year or more with a range of sequential experiments, we can now do in one single experiment," Professor Abell says.

 

The research has been published in the journal Chemical Science and is in collaboration¹⁸ with researchers at Monash University and Adelaide's Women's and Children's Hospital.

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