title: The Bacillus subtilis GntR family repressor YtrA responds to cell wall antibiotics.
abstract: The transglycosylation step of cell wall synthesis is a prime antibiotic target because it is essential and specific to bacteria. Two antibiotics, ramoplanin and moenomycin, target this step by binding to the substrate lipid II and the transglycosylase enzyme, respectively. Here, we compare the ramoplanin and moenomycin stimulons in the Gram-positive model organism Bacillus subtilis. Ramoplanin strongly induces the LiaRS two-component regulatory system, while moenomycin almost exclusively induces genes that are part of the regulon of the extracytoplasmic function (ECF) σ factor σ(M). Ramoplanin additionally induces the ytrABCDEF and ywoBCD operons, which are not part of a previously characterized antibiotic-responsive regulon. Cluster analysis reveals that these two operons are selectively induced by a subset of cell wall antibiotics that inhibit lipid II function or recycling. Repression of both operons requires YtrA, which recognizes an inverted repeat in front of its own operon and in front of ywoB. These results suggest that YtrA is an additional regulator of cell envelope stress responses.
authors.affiliation: Department of Microbiology, Cornell University, Ithaca, New York 14853-8101 14853-8101, USA.
authors.forename: Letal I
authors.initials: LI
authors.lastname: Salzberg
authors.forename: Yun
authors.initials: Y
authors.lastname: Luo
authors.forename: Anna-Barbara
authors.initials: AB
authors.lastname: Hachmann
authors.forename: Thorsten
authors.initials: T
authors.lastname: Mascher
authors.forename: John D
authors.initials: JD
authors.lastname: Helmann
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001412:Bacillus subtilis / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D002473:Cell Wall / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D047630:Depsipeptides / Q000494:pharmacology*; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects*; D009844:Oligosaccharides / Q000494:pharmacology*; D009876:Operon / Q000187:drug effects; D018085:Regulon / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D047630:Depsipeptides; D009844:Oligosaccharides; C041438:ramoplanin; C419802:moenomycin