@article{122721,
  keywords = {Protein Unfolding, Escherichia coli, Transcription Factors, Membrane Proteins, Escherichia coli Proteins, Endopeptidases, Bacterial Outer Membrane Proteins},
  author = {Anna Konovalova and Marcin Grabowicz and Carl Balibar and Juliana Malinverni and Ronald Painter and Daniel Riley and Paul Mann and Hao Wang and Charles Garlisi and Brad Sherborne and Nathan Rigel and Dante Ricci and Todd Black and Terry Roemer and Thomas Silhavy and Scott Walker},
  title = {Inhibitor of intramembrane protease RseP blocks the σ response causing lethal accumulation of unfolded outer membrane proteins},
  abstract = {<p>The outer membrane (OM) of Gram-negative bacteria forms a robust permeability barrier that blocks entry of toxins and antibiotics. Most OM proteins (OMPs) assume a β-barrel fold, and some form aqueous channels for nutrient uptake and efflux of intracellular toxins. The Bam machine catalyzes rapid folding and assembly of OMPs. Fidelity of OMP biogenesis is monitored by the σ stress response. When OMP folding defects arise, the proteases DegS and RseP act sequentially to liberate σ into the cytosol, enabling it to activate transcription of the stress regulon. Here, we identify batimastat as a selective inhibitor of RseP that causes a lethal decrease in σ activity in , and we further identify RseP mutants that are insensitive to inhibition and confer resistance. Remarkably, batimastat treatment allows the capture of elusive intermediates in the OMP biogenesis pathway and offers opportunities to better understand the underlying basis for σ essentiality.</p>
},
  year = {2018},
  journal = {Proc Natl Acad Sci U S A},
  volume = {115},
  pages = {E6614-E6621},
  month = {07/2018},
  issn = {1091-6490},
  doi = {10.1073/pnas.1806107115},
  language = {eng},
}