title: Antimicrobial peptides activate the Rcs regulon through the outer membrane lipoprotein RcsF.
abstract: Salmonella enterica species are exposed to envelope stresses due to their environmental and infectious lifestyles. Such stresses include amphipathic cationic antimicrobial peptides (CAMPs), and resistance to these peptides is an important property for microbial virulence for animals. Bacterial mechanisms used to sense and respond to CAMP-induced envelope stress include the RcsFCDB phosphorelay, which contributes to survival from polymyxin B exposure. The Rcs phosphorelay includes two inner membrane (IM) proteins, RcsC and RcsD; the response regulator RcsB; the accessory coregulator RcsA; and an outer membrane bound lipoprotein, RcsF. Transcriptional activation of the Rcs regulon occurred within minutes of exposure to CAMP and during the first detectable signs of CAMP-induced membrane disorder. Rcs transcriptional activation by CAMPs required RcsF and preservation of its two internal disulfide linkages. The rerouting of RcsF to the inner membrane or its synthesis as an unanchored periplasmic protein resulted in constitutive activation of the Rcs regulon and RcsCD-dependent phosphorylation. These findings suggest that RcsFCDB activation in response to CAMP-induced membrane disorder is a result of a change in structure or availability of RcsF to the IM signaling constituents of the Rcs phosphorelay.
authors.affiliation: Molecular and Cellular Biology Program, University of Washington, Seattle, WA 98195, USA.
authors.forename: Carol
authors.initials: C
authors.lastname: Farris
authors.forename: Sarah
authors.initials: S
authors.lastname: Sanowar
authors.forename: Martin W
authors.initials: MW
authors.lastname: Bader
authors.forename: Richard
authors.initials: R
authors.lastname: Pfuetzner
authors.forename: Samuel I
authors.initials: SI
authors.lastname: Miller
mesh_terms: D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects / Q000235:genetics; D008074:Lipoproteins / Q000235:genetics / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011485:Protein Binding; D018085:Regulon / Q000235:genetics / Q000502:physiology; D019779:Salmonella enterica / Q000187:drug effects / Q000235:genetics / Q000378:metabolism
chemical_list: D023181:Antimicrobial Cationic Peptides; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D008074:Lipoproteins