An Accurate In Vitro Model of the E. coli Envelope |
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| Authors: | Dr. Luke A. Clifton Dr. Stephen A. Holt Dr. Arwel V. Hughes Dr. Emma L. Daulton Dr. Wanatchaporn Arunmanee Dr. Frank Heinrich Dr. Syma Khalid Damien Jefferies Dr. Timothy R. Charlton Dr. John R. P. Webster Dr. Christian J. Kinane Prof. Jeremy H. Lakey |
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| Affiliation: | 1. ISIS Pulsed Neutron and Muon Source, Science and Technology Facilities Council, Rutherford Appleton Laboratory, Harwell Oxford Campus, Didcot, Oxfordshire, OX11 OQX (UK);2. Bragg Institute, Australian Nuclear Science and Technology Organisation, Locked Bag 2001, Kirrawee DC, NSW 2232 (Australia);3. Institute for Cell and Molecular Biosciences, Newcastle University, Framlington Place, Newcastle upon Tyne, NE2 4HH (UK);4. Department of Physics, Carnegie Mellon University, 5000 Forbes Ave. Pittsburgh, PA 15213 (USA);5. National Institute of Standards and Technology Center for Neutron Research, Gaithersburg, MD 20899 (USA);6. School of Chemistry, University of Southampton, Southampton SO17 1BJ (UK) |
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| Abstract: | Gram‐negative bacteria are an increasingly serious source of antibiotic‐resistant infections, partly owing to their characteristic protective envelope. This complex, 20 nm thick barrier includes a highly impermeable, asymmetric bilayer outer membrane (OM), which plays a pivotal role in resisting antibacterial chemotherapy. Nevertheless, the OM molecular structure and its dynamics are poorly understood because the structure is difficult to recreate or study in vitro. The successful formation and characterization of a fully asymmetric model envelope using Langmuir–Blodgett and Langmuir–Schaefer methods is now reported. Neutron reflectivity and isotopic labeling confirmed the expected structure and asymmetry and showed that experiments with antibacterial proteins reproduced published in vivo behavior. By closely recreating natural OM behavior, this model provides a much needed robust system for antibiotic development. |
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| Keywords: | antibiotics drug discovery Gram‐negative bacteria membranes structure– activity relationships |
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