title: Involvement and necessity of the Cpx regulon in the event of aberrant beta-barrel outer membrane protein assembly.
abstract: The Cpx and sigma(E) regulons help maintain outer membrane integrity; the Cpx pathway monitors the biogenesis of cell surface structures, such as pili, while the sigma(E) pathway monitors the biogenesis of beta-barrel outer membrane proteins (OMPs). In this study we revealed the importance of the Cpx regulon in the event of beta-barrel OMP mis-assembly, by utilizing mutants expressing either a defective beta-barrel OMP assembly machinery (Bam) or assembly defective beta-barrel OMPs. Analysis of specific mRNAs showed that Delta cpxR bam double mutants failed to induce degP expression beyond the wild type level, despite activation of the sigma(E) pathway. The synthetic conditional lethal phenotype of Delta cpxR in mutant Bam or beta-barrel OMP backgrounds was reversed by wild type DegP expressed from a heterologous plasmid promoter. Consistent with the involvement of the Cpx regulon in the event of aberrant beta-barrel OMP assembly, the expression of cpxP, the archetypal member of the cpx regulon, was upregulated in defective Bam backgrounds or in cells expressing a single assembly-defective beta-barrel OMP species. Together, these results showed that both the Cpx and sigma(E) regulons are required to reduce envelope stress caused by aberrant beta-barrel OMP assembly, with the Cpx regulon principally contributing by controlling degP expression.
authors.affiliation: School of Life Sciences, Arizona State University, Tempe, AZ 85287, USA.
authors.forename: Henri
authors.initials: H
authors.lastname: Gerken
authors.forename: Owen P
authors.initials: OP
authors.lastname: Leiser
authors.forename: Drew
authors.initials: D
authors.lastname: Bennion
authors.forename: Rajeev
authors.initials: R
authors.lastname: Misra
mesh_terms: D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry* / Q000378:metabolism*; D001426:Bacterial Proteins / Q000378:metabolism; D004926:Escherichia coli / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism; D033903:Periplasmic Proteins / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism; D018085:Regulon; D012697:Serine Endopeptidases / Q000378:metabolism; D012808:Sigma Factor / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D006360:Heat-Shock Proteins; D033903:Periplasmic Proteins; D012808:Sigma Factor; C063202:sporulation-specific sigma factors; C085504:CpxR protein, Bacteria; D011494:Protein Kinases; C490475:CpxA protein, E coli; C061682:DegP protease; D012697:Serine Endopeptidases