TY - JOUR
T1 - An Accurate in Vitro Model of the E. coli Envelope
AU - Clifton, Luke A.
AU - Holt, Stephen A.
AU - Hughes, Arwel V.
AU - Daulton, Emma L.
AU - Arunmanee, Wanatchaporn
AU - Heinrich, Frank
AU - Khalid, Syma
AU - Jefferies, Damien
AU - Charlton, Timothy R.
AU - Webster, John R.P.
AU - Kinane, Christian J.
AU - Lakey, Jeremy H.
N1 - Publisher Copyright:
© 2015 The Authors. Published by Wiley-VCH Verlag GmbH and Co. KGaA. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
PY - 2015/10/1
Y1 - 2015/10/1
N2 - 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.
AB - 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.
KW - Gram-negative bacteria
KW - antibiotics
KW - drug discovery
KW - membranes
KW - structure-activity relationships
UR - http://www.scopus.com/inward/record.url?scp=84942826141&partnerID=8YFLogxK
U2 - 10.1002/anie.201504287
DO - 10.1002/anie.201504287
M3 - Article
C2 - 26331292
AN - SCOPUS:84942826141
SN - 1433-7851
VL - 54
SP - 11952
EP - 11955
JO - Angewandte Chemie - International Edition
JF - Angewandte Chemie - International Edition
IS - 41
ER -