title: A novel two-component regulatory system in Bacillus subtilis for the survival of severe secretion stress.
abstract: The Gram-positive eubacterium Bacillus subtilis is well known for its high capacity to secrete proteins into the environment. Even though high-level secretion of proteins is an efficient process, it imposes stress on the cell. The present studies were aimed at the identification of systems required to combat this so-called secretion stress. A two-component regulatory system, named CssR-CssS, was identified, which bears resemblance to the CpxR-CpxA system of Escherichia coli. The results show that the CssR/S system is required for the cell to survive the severe secretion stress caused by a combination of high-level production of the alpha-amylase AmyQ and reduced levels of the extracytoplasmic folding factor PrsA. As shown with a prsA3 mutation, the Css system is required to degrade misfolded exported proteins at the membrane-cell wall interface. This view is supported by the observation that transcription of the htrA gene, encoding a predicted membrane-bound protease of B. subtilis, is strictly controlled by CssS. Notably, CssS represents the first identified sensor for extracytoplasmic protein misfolding in a Gram-positive eubacterium. In conclusion, the results show that quality control systems for extracytoplasmic protein folding are not exclusively present in the periplasm of Gram-negative eubacteria, but also in the Gram-positive cell envelope.
authors.affiliation: Laboratory of Vaccine Development, National Public Health Institute, FIN-00300, Helsinki, Finland.
authors.forename: H L
authors.initials: HL
authors.lastname: Hyyryläinen
authors.forename: A
authors.initials: A
authors.lastname: Bolhuis
authors.forename: E
authors.initials: E
authors.lastname: Darmon
authors.forename: L
authors.initials: L
authors.lastname: Muukkonen
authors.forename: P
authors.initials: P
authors.lastname: Koski
authors.forename: M
authors.initials: M
authors.lastname: Vitikainen
authors.forename: M
authors.initials: M
authors.lastname: Sarvas
authors.forename: Z
authors.initials: Z
authors.lastname: Prágai
authors.forename: S
authors.initials: S
authors.lastname: Bron
authors.forename: J M
authors.initials: JM
authors.lastname: van Dijl
authors.forename: V P
authors.initials: VP
authors.lastname: Kontinen
mesh_terms: D001412:Bacillus subtilis / Q000235:genetics / Q000254:growth & development / Q000502:physiology*; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D006360:Heat-Shock Proteins; D033903:Periplasmic Proteins; D017510:Protein Folding; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D000516:alpha-Amylases / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D006360:Heat-Shock Proteins; D033903:Periplasmic Proteins; D000516:alpha-Amylases; C061682:DegP protease; D012697:Serine Endopeptidases