title: The peptide chain release factor methyltransferase PrmC is essential for pathogenicity and environmental adaptation of Pseudomonas aeruginosa PA14.
abstract: Pseudomonas aeruginosa pathogenicity and its capability to adapt to multiple environments are dependent on the production of diverse virulence factors, controlled by the sophisticated quorum sensing (QS) network of P. aeruginosa. To better understand the molecular mechanisms that underlie this adaptation we searched for novel key regulators of virulence factor production by screening a PA14 transposon mutant library for potential candidates acting downstream of the unique 2-alkyl-4-quinolone (AQ) QS system of P. aeruginosa. We focused the work on a protein named HemK with high homology to PrmC of Escherichia coli displaying a similar enzymatic activity (therefore also referred to as PrmC). In this study, we demonstrate that PrmC is an S-adenosyl-l-methionine (AdoMet)-dependent methyltransferase of peptide chain release factors (RFs) essential for the expression of several virulence factors, such as pyocyanin, rhamnolipids and the type III-secreted toxin ExoT. Furthermore, the PA14_prmC mutant strain is unable to grow under anoxic conditions and has a significantly reduced pathogenicity in the infection model Galleria mellonella. Along with transcriptomic and proteomic analyses, the presented data indicate that the methylation of RFs in P. aeruginosa seems to have a global effect on cellular processes related to the virulence of this nosocomial pathogen.
authors.affiliation: Department of Molecular Bacteriology, Helmholtz Center for Infection Research, Braunschweig, Germany. Christian.pustelny@helmholtz-hzi.de
authors.forename: Christian
authors.initials: C
authors.lastname: Pustelny
authors.forename: Stephan
authors.initials: S
authors.lastname: Brouwer
authors.forename: Mathias
authors.initials: M
authors.lastname: Müsken
authors.forename: Agata
authors.initials: A
authors.lastname: Bielecka
authors.forename: Andreas
authors.initials: A
authors.lastname: Dötsch
authors.forename: Manfred
authors.initials: M
authors.lastname: Nimtz
authors.forename: Susanne
authors.initials: S
authors.lastname: Häussler
mesh_terms: D000222:Adaptation, Physiological / Q000235:genetics*; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D007814:Larva / Q000382:microbiology; D008780:Methyltransferases / Q000235:genetics / Q000378:metabolism*; D009036:Moths / Q000382:microbiology; D009154:Mutation; D040901:Proteomics; D011550:Pseudomonas aeruginosa / Q000201:enzymology* / Q000235:genetics / Q000254:growth & development / Q000472:pathogenicity; D053038:Quorum Sensing / Q000235:genetics; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D037521:Virulence Factors; D008780:Methyltransferases