A novel two-component regulatory system in Bacillus subtilis for the survival of severe secretion stress

Mol Microbiol. 2001 Sep;41(5):1159-72. doi: 10.1046/j.1365-2958.2001.02576.x.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacillus subtilis / genetics
  • Bacillus subtilis / growth & development
  • Bacillus subtilis / physiology*
  • Bacterial Proteins / genetics*
  • Bacterial Proteins / metabolism*
  • Gene Expression Regulation, Bacterial*
  • Heat-Shock Proteins*
  • Periplasmic Proteins*
  • Protein Folding
  • Serine Endopeptidases / genetics
  • Serine Endopeptidases / metabolism
  • Transcription, Genetic
  • alpha-Amylases / metabolism*


  • Bacterial Proteins
  • Heat-Shock Proteins
  • Periplasmic Proteins
  • alpha-Amylases
  • DegP protease
  • Serine Endopeptidases