The Super-antibiotics That Could Save Us.
The alarming increase of pathogenic bacteria that are resistant to multiple antibiotics is now recognised as a major health issue fuelling demand for new drugs. Bacterial resistance is often caused by molecular changes at the bacterial surface, which alter the nature of specific drug-target interactions. The University College of London team identified a novel mechanism by which drug-target interactions in resistant bacteria can be enhanced. They examined the surface forces generated by four antibiotics; vancomycin, ristomycin, chloroeremomycin and oritavancin against drug-susceptible and drug-resistant targets on a cantilever and demonstrated significant differences in mechanical response when drug-resistant targets are challenged with different antibiotics although no significant differences were observed when using susceptible targets. Remarkably, the binding affinity for oritavancin against drug-resistant targets (70 nM) was found to be 11,000 times stronger than for vancomycin (800 μM), a powerful antibiotic used as the last resort treatment for streptococcal and staphylococcal bacteria including methicillin-resistant Staphylococcus aureus (MRSA). Using an exactly solvable model, which takes into account the solvent and membrane effects, the team demonstrated that drug-target interactions are strengthened by pronounced polyvalent interactions catalysed by the surface itself. These findings further enhance the understanding of antibiotic mode of action and will enable development of more effective therapies. Credit: Publish paper Surface Mediated Cooperative Interactions of Drugs Enhance Mechanical Forces for Antibiotic Action by Joseph W. Ndieyira et al.
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