Gene Expression and Physiological Role of Pseudomonas aeruginosa Methionine Sulfoxide Reductases during Oxidative Stress

Pseudomonas aeruginosa PAO1 has two differentially expressed methionine sulfoxide reductase genes:msrA (PA5018) andmsrB (PA2827). ThemsrA gene is expressed constitutively at a high level throughout all growth phases, whereasmsrB expression is highly induced by oxidative stress, such as sodium hypochlorite (NaOCl) treatment. Inactivation of eithermsrA ormsrB or both genes (msrA msrB mutant) rendered the mutants less resistant than the parental PAO1 strain to oxidants such as NaOCl and H2 O2 . Unexpectedly,msr mutants have disparate resistance patterns when exposed to paraquat, a superoxide generator. ThemsrA mutant had a higher paraquat resistance level than themsrB mutant, which had a lower paraquat resistance level than the PAO1 strain. The expression levels ofmsrA showed an inverse correlation with the paraquat resistance level, and this atypical paraquat resistance pattern was not observed withmsrB . Virulence testing using aDrosophila melanogaster model revealed that themsrA ,msrB , and, to a greater extent,msrA msrB double mutants had an attenuated virulence phenotype. The data indicate thatmsrA andmsrB are essential genes for oxidative stress protection and bacterial virulence. The pattern of expression and mutant phenotypes ofP. aeruginosa msrA andmsrB differ from previously characterizedmsr genes from other bacteria. Thus, as highly conserved genes, themsrA andmsrB have diverse expression patterns and physiological roles that depend on the environmental niche where the bacteria thrive.