How do bacterial membranes resist polymyxin antibiotics?

In our recent Communications Biology article, we reported on the biophysical mechanism of resistance for polymyxin antibiotics in bacterial membranes. The emergence of plasmid-borne colistin resistance poses a threat to our last line of defense against many pathogens. Here, we outline the current understanding of mcr-1-mediated polymyxin resistance, and propose future directions for membrane-targeting antibiotic research.