A novel class of antibiotic being explored at the University of Adelaide has shown potential in the fight against bacterial antibiotic resistance. Professor Andrew Abell and his colleagues have engineered antibiotic compounds that target a key metabolic enzyme, biotin protein ligase, instead of the cell membrane, which is a common target of some existing antibiotics. By changing the target of the antibiotic, it is hoped that a broad range of antibiotic resistant bacteria will again be susceptible.
To create these antibiotics, an innovative approach called 'in situ click chemistry' was used. This method involves presenting precursor inhibitory molecules to the bacteria in such a way that causes the bacterial target to builds the inhibitory molecule and then binds to it. So, the bacteria is effectively choosing to create a destructive molecule. The continued production and binding of this molecule to the metabolic enzyme both inactivates the enzyme, and disrupts the life cycle of the bacterial cell.
Although these antibiotics have yet to be tested in animals, the in vitro results are promising. Researchers at the University of Adelaide have proven that the their engineered compounds are inhibitory and can bind to the target enzyme. Additionally, they have shown that their antibiotic compounds can stop growth in a wide range bacteria. To further investigate the potential clinical performance and efficacy of these antibiotics, an animal model needs to be established and explored. There is still much work to be done, but insight has been gained into a new class of antibiotic that could one day join the battle against bacterial antibiotic resistance.