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UCL and Imperial Capture How Polymyxin B Forces Gram-Negative Bacteria to Shed Their Armor

The study links the drug’s killing to bacterial metabolism, pointing to tactics that wake dormant cells.

Overview

  • Using atomic force microscopy on single E. coli cells, researchers recorded rapid surface bulges followed by frantic outer-membrane production and shedding that opened gaps for antibiotic entry.
  • Dormant cells with halted membrane biogenesis resisted damage, whereas metabolically active cells were efficiently killed by the drug.
  • Providing sugar reawakened dormant E. coli and restored susceptibility, with killing observed after about 15 minutes.
  • Under conditions where killing occurred, the team measured increased release of outer-membrane material and widespread protrusions; when bacteria were inactive, the antibiotic bound with little structural disruption.
  • Published in Nature Microbiology, the work underscores that polymyxins are last-resort agents and supports reassessing efficacy tests and pursuing combinations that stimulate membrane production or rouse persister cells.