Bacteriocin biophysics: From protein–protein interaction models to navigators of the bacterial cell envelope

Bacteriocins are toxins deployed by bacteria to kill their competitors. Here, I reflect on my laboratory's work on protein bacteriocins and their immunity proteins from Gram-negative bacteria. We uncovered the structural and biophysical principles that underpin the 10-log stability range of protective immunity proteins for cytotoxic nuclease bacteriocins. We went on to elucidate how bacteriocins that kill Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae subvert outer membrane proteins and periplasmic energy transduction systems to drive their import. We leveraged our understanding of bacteriocin structure and function to probe the nature of the bacterial outer membrane. These studies revealed the outer membrane of E. coli to be an asymmetric proteolipid membrane, not an asymmetric lipid membrane as has been accepted dogma for the last 50 years. I contextualize the work with background on my career, collaborations, and academic leadership roles that influenced my development as a scientist.