Two FtsH Proteases Contribute to Fitness and Adaptation of Pseudomonas aeruginosa Clone C Strains

Pseudomonas aeruginosais an environmental bacterium and a nosocomial pathogenwith clone C one of the most prevalent clonal groups. TheP. aeruginosaclone Cspecific genomic island PACGI-1 harbors a xenolog offtsHencoding a functionallydiverse membrane-spanning ATP-dependent metalloprotease on the core genome. Inthe aquatic isolateP. aeruginosaSG17M, the core genome copyftsH1significantlyaffects growth and dominantly mediates a broad range of phenotypes, such assecretion of secondary metabolites, swimming and twitching motility and resistance toaminoglycosides, while the PACGI-1 xenologftsH2backs up the phenotypes in theftsH1mutant background. The two proteins, with conserved motifsfor disaggregaseand protease activity present in FtsH1 and FtsH2, have the ability to form homo- andhetero-oligomers withftsH2distinctively expressed in the late stationary phase ofgrowth. However, mainly FtsH1 degrades a major substrate, the heat shock transcriptionfactor RpoH. Pull-down experiments with substrate trap-variants inactive in proteolyticactivity indicate both FtsH1 and FtsH2 to interact with the inhibitory protein HflC,while the phenazine biosynthesis protein PhzC was identified as a substrate of FtsH1.In summary, as an exception inP. aeruginosa, clone C harbors two copies of theftsHmetallo-protease, which cumulatively are required for theexpression of a diversityof phenotypes.