TY - JOUR
T1 - Biophysical Impact of Lipid A Modification Caused by Mobile Colistin Resistance Gene on Bacterial Outer Membranes
AU - Ma, Wendong
AU - Jiang, Xukai
AU - Dou, Yujiang
AU - Zhang, Zhihong
AU - Li, Jian
AU - Yuan, Bing
AU - Yang, Kai
N1 - Funding Information:
This work is financially supported by the National Natural Science Foundation of China (Nos. 21774092, U1932121, and 21728502) and the Priority Academic Program Development (PAPD) of Jiangsu Higher Education Institutions.
Publisher Copyright:
© 2021 American Chemical Society. All rights reserved.
PY - 2021/12/9
Y1 - 2021/12/9
N2 - Expression of mobile colistin resistance gene mcr-1 results in the addition of phosphoethanolamine (pEtN) to the lipid A headgroup in the bacterial outer membrane (OM) of Gram-negative bacteria, increasing the resistance to the last-line polymyxins. However, the potential biological consequences of such modification remain unclear. Using coarse-grained molecular simulations with quantitative lipidomics models, we discovered pEtN modification of the lipid A headgroup caused substantial changes to the morphology and physicochemical properties of the OM. Single-lipid level structural and energetic analyses revealed that this modification resulted in lipid A-pEtN adopting an abnormally twisted and slanted conformation with a closer packing state because of strengthened inter-lipid attraction. The consequent accumulation of lipid A-pEtN produced a negative curvature of the OM and altered the membrane's tension, fluidity, and rigidity. Our results provide a key mechanistic connection between mcr-1 expression and biophysical changes in the bacterial OM.
AB - Expression of mobile colistin resistance gene mcr-1 results in the addition of phosphoethanolamine (pEtN) to the lipid A headgroup in the bacterial outer membrane (OM) of Gram-negative bacteria, increasing the resistance to the last-line polymyxins. However, the potential biological consequences of such modification remain unclear. Using coarse-grained molecular simulations with quantitative lipidomics models, we discovered pEtN modification of the lipid A headgroup caused substantial changes to the morphology and physicochemical properties of the OM. Single-lipid level structural and energetic analyses revealed that this modification resulted in lipid A-pEtN adopting an abnormally twisted and slanted conformation with a closer packing state because of strengthened inter-lipid attraction. The consequent accumulation of lipid A-pEtN produced a negative curvature of the OM and altered the membrane's tension, fluidity, and rigidity. Our results provide a key mechanistic connection between mcr-1 expression and biophysical changes in the bacterial OM.
UR - http://www.scopus.com/inward/record.url?scp=85120647903&partnerID=8YFLogxK
U2 - 10.1021/acs.jpclett.1c03295
DO - 10.1021/acs.jpclett.1c03295
M3 - Article
C2 - 34817187
AN - SCOPUS:85120647903
SN - 1948-7185
VL - 12
SP - 11629
EP - 11635
JO - Journal of Physical Chemistry Letters
JF - Journal of Physical Chemistry Letters
IS - 48
ER -