PRJNA856786
Synthetic ion transporter that targets s. aureus
New drugs are desperately needed to address the growing health crisis associated with antibiotics resistant bacteria, particularly methicillin resistant S. aureus (MRSA). Adding to the challenge is the prevalence of dormant persisters and biofilms which are highly tolerant to the conventional antibiotics. Ion homeostasis, which plays an important role in bacterial respiration, is an appealing target to control bacterial infections. However, it was impeded since previously reported ion transporters have indiscriminate toxicity between mammalian cells and bacteria. Here, we reported the synthetic cation transporters which had enhanced selectivity on MRSA over mammalian cells. Furthermore, they remarkably eliminate bacterial persisters, reduce established biofilm, prevent biofilm formation and suppress bacterial virulence toxins production. Analysis of their mode of action showed these ion transporters led to cytoplasmic acidification and calcium influx, which triggered autolysis acceleration. With further optimization, we believe these synthetic ion transporters have great potential as promising antibiotics to address bacterial infections.