An orphan <i>cbb</i>₃-type cytochrome oxidase subunit supports <i>Pseudomonas aeruginosa</i> biofilm growth and virulence.

Abstract

Hypoxia is a common challenge faced by bacteria during associations with hosts due in part to the formation of densely packed communities (biofilms). <i>cbb</i>₃-type cytochrome <i>c</i> oxidases, which catalyze the terminal step in respiration and have a high affinity for oxygen, have been linked to bacterial pathogenesis. The pseudomonads are unusual in that they often contain multiple full and partial (i.e. 'orphan') operons for <i>cbb</i>₃-type oxidases and oxidase subunits. Here, we describe a unique role for the orphan catalytic subunit CcoN4 in colony biofilm development and respiration in the opportunistic pathogen <i>Pseudomonas aeruginosa</i> PA14. We also show that CcoN4 contributes to the reduction of phenazines, antibiotics that support redox balancing for cells in biofilms, and to virulence in a <i>Caenorhabditis elegans</i> model of infection. These results highlight the relevance of the colony biofilm model to pathogenicity and underscore the potential of <i>cbb</i>₃-type oxidases as therapeutic targets.