Abstract:
: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 σE stress response. When OMP folding defects arise, the proteases DegS and RseP act sequentially to liberate σE 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 σE activity in Escherichia coli, 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 σE essentiality.
journal_name
Proc Natl Acad Sci U S Aauthors
Konovalova A,Grabowicz M,Balibar CJ,Malinverni JC,Painter RE,Riley D,Mann PA,Wang H,Garlisi CG,Sherborne B,Rigel NW,Ricci DP,Black TA,Roemer T,Silhavy TJ,Walker SSdoi
10.1073/pnas.1806107115subject
Has Abstractpub_date
2018-07-10 00:00:00pages
E6614-E6621issue
28eissn
0027-8424issn
1091-6490pii
1806107115journal_volume
115pub_type
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