Expression of multiplecbb3cytochromecoxidase isoforms by combinations of multiple isosubunits inPseudomonas aeruginosa

Abstract

The ubiquitous opportunistic human pathogenPseudomonas aeruginosahas five terminal oxidases for aerobic respiration and uses them under different growth conditions. Two of them arecbb3-type cytochromecoxidases encoded by the gene clustersccoN1O1Q1P1andccoN2O2Q2P2, which are the main terminal oxidases under high- and low-oxygen conditions, respectively.P. aeruginosaalso has two orphan gene clusters,ccoN3Q3andccoN4Q4, encoding the core catalytic CcoN isosubunits, but the roles of these genes have not been clarified. We found that 16 activecbb3isoforms could be produced by combinations of four CcoN, two CcoO, and two CcoP isosubunits. The CcoN3- or CcoN4-containing isoforms were produced in the WT cell membrane in response to nitrite and cyanide, respectively. The strains carrying these isoforms were more resistant to nitrite or cyanide under low-oxygen conditions. These results indicate thatP. aeruginosagains resistance to respiratory inhibitors using multiplecbb3isoforms with different features, which are produced through exchanges of multiple core catalytic isosubunits.