title: In-depth profiling of the LiaR response of Bacillus subtilis.
abstract: The Lia system, a cell envelope stress response module of Bacillus subtilis, is comprised of the LiaRS two-component system and a membrane-anchored inhibitor protein, LiaF. It is highly conserved in the Firmicutes bacteria, and all orthologs investigated so far are activated by cell wall antibiotics. In response to envelope stress, the systems in Firmicutes cocci induce the expression of a number of genes that are involved in conferring resistance against its inducers. In contrast, a complete picture of the LiaR regulon of B. subtilis is still missing and no phenotypes could be associated with mutants lacking LiaRS. Here, we performed genome-wide transcriptomic, proteomic, and in-depth phenotypic profiling of constitutive "Lia ON" and "Lia OFF" mutants to obtain a comprehensive picture of the Lia response of Bacillus subtilis. In addition to the known targets liaIH and yhcYZ-yhdA, we identified ydhE as a novel gene affected by LiaR-dependent regulation. The results of detailed follow-up gene expression studies, together with proteomic analysis, demonstrate that the liaIH operon represents the only relevant LiaR target locus in vivo. It encodes a small membrane protein (LiaI) and a phage shock protein homolog (LiaH). LiaH forms large oligomeric rings reminiscent of those described for Escherichia coli PspA or Arabidopsis thaliana Vipp1. The results of comprehensive phenotype studies demonstrated that the gene products of the liaIH operon are involved in protecting the cell against oxidative stress and some cell wall antibiotics. Our data suggest that the LiaFSR system of B. subtilis and, presumably, other Firmicutes bacilli coordinates a phage shock protein-like response.
authors.affiliation: Department of Biology I, Ludwig Maximilians University of Munich, Grosshaderner Str 2-4, D-82152 Planegg-Martinsried, Germany.
authors.forename: Diana
authors.initials: D
authors.lastname: Wolf
authors.forename: Falk
authors.initials: F
authors.lastname: Kalamorz
authors.forename: Tina
authors.initials: T
authors.lastname: Wecke
authors.forename: Anna
authors.initials: A
authors.lastname: Juszczak
authors.forename: Ulrike
authors.initials: U
authors.lastname: Mäder
authors.forename: Georg
authors.initials: G
authors.lastname: Homuth
authors.forename: Sina
authors.initials: S
authors.lastname: Jordan
authors.forename: Janine
authors.initials: J
authors.lastname: Kirstein
authors.forename: Michael
authors.initials: M
authors.lastname: Hoppert
authors.forename: Birgit
authors.initials: B
authors.lastname: Voigt
authors.forename: Michael
authors.initials: M
authors.lastname: Hecker
authors.forename: Thorsten
authors.initials: T
authors.lastname: Mascher
mesh_terms: D001412:Bacillus subtilis / Q000235:genetics* / Q000648:ultrastructure; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D015152:Blotting, Northern; D002850:Chromatography, Gel; D015180:Electrophoresis, Gel, Two-Dimensional; D015964:Gene Expression Regulation, Bacterial / Q000235:genetics / Q000502:physiology; D008563:Membrane Lipids / Q000235:genetics / Q000378:metabolism*; D046529:Microscopy, Electron, Transmission; D016254:Mutagenesis, Insertional; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic / Q000235:genetics; D017384:Sequence Deletion
chemical_list: D001426:Bacterial Proteins; C490532:LiaRS protein, Bacillus subtilis; D008563:Membrane Lipids