التفاصيل البيبلوغرافية
| العنوان: |
Combining Cell Envelope Stress Reporter Assays in a Screening Approach to Identify BAM Complex Inhibitors |
| المؤلفون: |
Maurice Steenhuis (10968314), Federico Corona (10968317), Corinne M. ten Hagen-Jongman (10968320), Waldemar Vollmer (175986), Dominique Lambin (9941681), Philippe Selhorst (4799031), Hugo Klaassen (2035108), Matthias Versele (10968323), Patrick Chaltin (1656292), Joen Luirink (243945) |
| سنة النشر: |
2021 |
| المجموعة: |
Smithsonian Institution: Digital Repository |
| مصطلحات موضوعية: |
Biophysics, Biochemistry, Microbiology, Pharmacology, Biological Sciences not elsewhere classified, Chemical Sciences not elsewhere classified, OMP biogenesis mutants, compound 2, novel target, BAM-dependent OMP, β- barrel assembly machine, screening approach, refolding assay, Cell Envelope Stress Reporter Assays, 316 953, σ E, antibiotic, β- barrel type OM protein, intracellular heat-shock response, Escherichia coli, compounds 2, Identify BAM Complex Inhibitors, inhibitor, Gram-negative bacteria, Rcs stress, OM integrity, 316 953 compounds, Rcs stress responses, cell envelope σ E, permeability barrier |
| الوصف: |
The development of new antibiotics is particularly problematic in Gram-negative bacteria due to the presence of the outer membrane (OM), which serves as a permeability barrier. Recently, the β-barrel assembly machine (BAM), located in the OM and responsible for β-barrel type OM protein (OMP) assembly, has been validated as a novel target for antibiotics. Here, we identified potential BAM complex inhibitors using a screening approach that reports on cell envelope σ E and Rcs stress in Escherichia coli . Screening a library consisting of 316 953 compounds yielded five compounds that induced σ E and Rcs stress responses, while not inducing the intracellular heat-shock response. Two of the five compounds (compounds 2 and 14) showed the characteristics of known BAM complex inhibitors: synergy with OMP biogenesis mutants, decrease in the abundance of various OMPs, and loss of OM integrity. Importantly, compound 2 also inhibited BAM-dependent OMP folding in an in vitro refolding assay using purified BAM complex reconstituted in proteoliposomes. |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
unknown |
| Relation: |
https://figshare.com/articles/journal_contribution/Combining_Cell_Envelope_Stress_Reporter_Assays_in_a_Screening_Approach_to_Identify_BAM_Complex_Inhibitors/14780015 |
| DOI: |
10.1021/acsinfecdis.0c00728.s001 |
| الاتاحة: |
https://doi.org/10.1021/acsinfecdis.0c00728.s001 |
| Rights: |
CC BY-NC 4.0 |
| رقم الانضمام: |
edsbas.1C5B18E2 |
| قاعدة البيانات: |
BASE |