title: Acid stress activation of the sigma(E) stress response in Salmonella enterica serovar Typhimurium.
abstract: The alternative sigma factor sigma(E) is activated by unfolded outer membrane proteins (OMPs) and plays an essential role in Salmonella pathogenesis. The canonical pathway of sigma(E) activation in response to envelope stress involves sequential proteolysis of the anti-sigma factor RseA by the PDZ proteases DegS and RseP. Here we show that sigma(E) in Salmonella enterica sv. Typhimurium can also be activated by acid stress. A sigma(E)-deficient mutant exhibits increased susceptibility to acid pH and reduced survival in an acidified phagosomal vacuole. Acid activation of sigma(E)-dependent gene expression is independent of the unfolded OMP signal or the DegS protease but requires processing of RseA by RseP. The RseP PDZ domain is indispensable for acid induction, suggesting that acid stress may disrupt an inhibitory interaction between RseA and the RseP PDZ domain to allow RseA proteolysis in the absence of antecedent action of DegS. These observations demonstrate a novel environmental stimulus and activation pathway for the sigma(E) regulon that appear to be critically important during Salmonella-host cell interactions.
authors.affiliation: Departments of Laboratory Medicine, University o9f Washington School of Medicine, Seattle, WA 98121, USA.
authors.forename: Cécile
authors.initials: C
authors.lastname: Muller
authors.forename: Iel-Soo
authors.initials: IS
authors.lastname: Bang
authors.forename: Jyoti
authors.initials: J
authors.lastname: Velayudhan
authors.forename: Joyce
authors.initials: J
authors.lastname: Karlinsey
authors.forename: Kai
authors.initials: K
authors.lastname: Papenfort
authors.forename: Jörg
authors.initials: J
authors.lastname: Vogel
authors.forename: Ferric C
authors.initials: FC
authors.lastname: Fang
mesh_terms: D000143:Acids / Q000378:metabolism*; D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism*; D002460:Cell Line; D015964:Gene Expression Regulation, Bacterial; D006863:Hydrogen-Ion Concentration; D051379:Mice; D009154:Mutation; D012329:RNA, Bacterial / Q000378:metabolism; D018085:Regulon; D012486:Salmonella typhimurium / Q000235:genetics / Q000378:metabolism*; D012808:Sigma Factor / Q000378:metabolism*; D013312:Stress, Physiological; D014617:Vacuoles / Q000382:microbiology
chemical_list: D000143:Acids; D001426:Bacterial Proteins; C066496:DegS protein, Bacteria; D012329:RNA, Bacterial; D012808:Sigma Factor; C111259:sigE protein, Bacteria