Abstract
Hypoxia is a common challenge faced by bacteria during associations with hosts due in part to the formation of densely packed communities (biofilms). cbb3-type cytochrome c 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 cbb3-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 Pseudomonas aeruginosa 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 Caenorhabditis elegans model of infection. These results highlight the relevance of the colony biofilm model to pathogenicity and underscore the potential of cbb3-type oxidases as therapeutic targets.
Highlights
Among the oxidants available for biological reduction, molecular oxygen (O2) provides the highest free energy yield
Our results indicate that isoforms containing the orphan subunit CcoN4 can support survival in biofilms via O2 and phenazine reduction and contribute to P. aeruginosa pathogenicity in a Caenorhabditis elegans ‘slow killing’ model of infection
We have previously reported that 3-day-old PA14 colony biofilms are hypoxic at depth (Dietrich et al, 2013) and that O2 availability is generally higher in thinner biofilms, such as those formed by the phenazine-null mutant Dphz
Summary
Among the oxidants available for biological reduction, molecular oxygen (O2) provides the highest free energy yield. This study shows that blocking terminal oxidases that contain CcoN4 can weaken P. aeruginosa and its ability to cause infections These types of terminal oxidases are only found in bacteria, which makes them attractive targets for potential drugs that would have minimal side effects on the host’s metabolism. The authors found that the products of ccoN3Q3 and ccoN4Q4 contributed resistance to nitrite and cyanide, respectively, during growth in liquid cultures under low-O2 conditions While these results provide insight into contributions of the cbb heterocomplexes to growth in liquid cultures, potential roles for N3- and N4-containing isoforms in biofilm growth and pathogenicity have yet to be explored. Our results indicate that isoforms containing the orphan subunit CcoN4 can support survival in biofilms via O2 and phenazine reduction and contribute to P. aeruginosa pathogenicity in a Caenorhabditis elegans ‘slow killing’ model of infection
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