Computationally designed pyocyanin demethylase acts synergistically with tobramycin to kill recalcitrant <i>Pseudomonas aeruginosa</i> biofilms
Chelsey M. VanDrisse, Rosalie Lipsh‐Sokolik, Olga Khersonsky, Sarel J. Fleishman, Dianne K. Newman
Abstract
Significance Pseudomonas aeruginosa is a major cause of hospital-acquired infections due to its formation of biofilms that are highly tolerant to antibiotics. Conventional drugs often fail to kill slowly growing biofilms because they do not target the mechanisms that sustain cells in this state; alternative biofilm control strategies are thus urgently needed. One way in which P. aeruginosa builds robust biofilms is through the production of redox-active phenazines such as pyocyanin. We identified an enzyme that degrades pyocyanin but were stymied in studying its potential to combat biofilms due to its poor expression yield. Here we show how protein design can stabilize the enzyme to improve purification yields, enabling physiological studies to reveal a novel enzyme’s therapeutic potential.