The company may have forgotten PBT2... But in the science world the interest is still going on
https://www.otago.ac.nz/healthsciences/news/news/otago0235933.html
Antimicrobial resistance (AMR) is a rapidly evolving global emergency. Professor Cook and his team have demonstrated that the zinc ionophore PBT2 can resensitise high-priority drug-resistant bacterial pathogens to multiple antimicrobial classes in vitro and in vivo. The mechanisms underpinning this resensitisation remain unknown but may hold the key to breathing life into antimicrobials that have become discarded due to widespread resistance. The researchers hypothesise that the dysregulation of metal ion homeostasis functionally impairs genetic and metabolic resistance pathways resulting in antimicrobial resensitisation. To address this hypothesis, they will use methicillin-resistant Staphylococcus aureus as a model system to elucidate the molecular determinants of PBT2-Zn mediated β-lactam (e.g. oxacillin) resensitisation. They will achieve this by combining complementary genetic, metabolic, and biochemical approaches to uncover the AMR breaking network triggered by PBT2-Zn. This study will increase our understanding of how changes in bacterial metal ion homeostasis trigger critical physiological and metabolic pathways to sensitise bacterial cells to antibiotics. Understanding this will provide essential insight into driving the development of unique antibiotic adjuvants for breaking AMR and provide a molecular framework for understanding AMR reversal more broadly in other bacterial pathogens.
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