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Biophysical Impact of Lipid A Modification Caused by Mobile Colistin Resistance Gene on Bacterial Outer Membranes

Wendong Ma1,2, Xukai Jiang3, Yujiang Dou1

  • 1School of Electronic Information, Dongguan Polytechnic, Dongguan, Guangdong 523808, China.

The Journal of Physical Chemistry Letters
|November 24, 2021
PubMed

Insights

The mobile colistin resistance gene mcr-1 alters bacterial outer membranes by adding phosphoethanolamine (pEtN) to lipid A. This modification changes membrane structure and properties, impacting bacterial resistance mechanisms.

Area of Science:

  • Microbiology
  • Biophysics
  • Structural Biology

Background:

  • The mobile colistin resistance gene *mcr-1* confers resistance to polymyxins by modifying lipid A.
  • The precise biophysical consequences of this modification on the bacterial outer membrane are not fully understood.

Purpose of the Study:

  • To investigate the structural and physicochemical effects of phosphoethanolamine (pEtN) modification on the bacterial outer membrane (OM).
  • To elucidate the mechanistic link between *mcr-1* expression and OM biophysical alterations.

Main Methods:

  • Coarse-grained molecular simulations.
  • Quantitative lipidomics models.
  • Single-lipid level structural and energetic analyses.

Main Results:

  • pEtN modification induced significant changes in OM morphology and properties.
  • Lipid A-pEtN adopted a twisted, slanted conformation with closer packing due to enhanced inter-lipid attraction.
  • Accumulation of lipid A-pEtN resulted in negative OM curvature, altered membrane tension, fluidity, and rigidity.

Conclusions:

  • *mcr-1* expression leads to substantial biophysical alterations in the Gram-negative bacterial outer membrane.
  • These changes provide a mechanistic understanding of how *mcr-1* impacts bacterial physiology and resistance.

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