The outer membrane (OM) excludes antibiotics such as vancomycin that kill gram-positive bacteria, and so is a major contributor to multidrug resistance in gram-negative bacteria. Yet, the OM is readily bypassed by protein bacteriocins, which are toxins released by bacteria to kill their neighbors during competition for resources. Discovered over 60 y ago, it has been a mystery how these proteins cross the OM to deliver their toxic payload. We have discovered how the bacteriocin pyocin S2 (pyoS2), which degrades DNA, enters Pseudomonas aeruginosa cells. PyoS2 tricks the iron transporter FpvAI into transporting it across the OM by a process that is remarkably similar to that used by its endogenous ligand, the siderophore ferripyoverdine.

Abstract