Taxonomic group: bacteria / Proteobacteria (Phylum: Proteobacteria)
Associated disease: cholera [ICD11: 1A00 , ICD11: XN7N1 ]
 
NCBI PubMed ID: 33600188
Publication DOI: 10.1021/acs.jpcb.0c09144
Journal NLM ID: 101157530
Publisher: Washington, DC: American Chemical Society
Correspondence: goran.widmalmsu.se; wonpillehigh.edu
Institutions: Department of Organic Chemistry, Arrhenius Laboratory, Stockholm University, SE-106 91 Stockholm, Sweden, School of Computational Sciences, Korea Institute for Advanced Study, Seoul 02455, Republic of Korea, Departments of Biological Sciences, Chemistry, Bioengineering, and Computer Science and Engineering, Lehigh University, Bethlehem, Pennsylvania 18015, United States, School of Mathematics, Physics, and Statistics, Shanghai University of Engineering Science, Shanghai 201620, China

Lipopolysaccharides (LPS) present in the outer leaflet of Gram-negative bacterial outer membranes protect the bacteria from external threats and influence antibiotic permeability as well as immune system recognition. The structure of lipid A, the anchor of an LPS molecule to the outer membrane, can make direct influences on membrane properties. Particularly, in Vibrio cholerae, a Gram-negative bacterium responsible for cholera, a severe diarrheal disease, modifications of lipid A structures grant antibiotic resistance and are a primary factor that led to the current cholera pandemic. However, the difference in structural properties incurred by such modifications has not been fully explored. In this work, five symmetric bilayer systems comprised of distinct lipid A structures of Vibrio cholerae LPS with O1 O-antigen were modeled and simulated to explore influences of different lipid A types on membrane properties. All-atom molecular dynamics simulations reveal that membrane properties such as hydrophobic thickness, acyl chain order parameter, and area per lipid are largely impacted by lipid A modifications due to differences in composition and acyl chain distortions. The modified lipid A is also less negatively charged, which possibly reveals a resistance mechanism to cationic antimicrobial peptide evasion. These findings present a possible explanation for Vibrio cholerae's immune system evasion properties and establish the differences between the lipid A types, which should be of use for any future study of the Gram-negative bacteria.

Lipopolysaccharide, structure, Vibrio cholerae, bilayer, molecular dynamics simulations, Lipid A modifications, bacterial outer membrane

Structure type: oligomer
Location inside paper: p. 2106, Fig. 1, lipid A type 2
Compound class: lipid A
Contained glycoepitopes: IEDB_135394,IEDB_135515,IEDB_141807,IEDB_151531,IEDB_176772
 
Methods: MD simulations, CHARMM-GUI Membrane Builder
Comments, role: lipid A type 2
3D data: 3D data
 
Related record ID(s): 9693, 9694, 9695, 10900
NCBI Taxonomy refs (TaxIDs): 127906
Show glycosyltransferases
 

Convert structure to SMILES & 3D GlycoCT β-test WURCS 2.0 GLYCAM GlycoCT (external) GlycoCT XML (ext) GlydeII XML LinUCS Fragmentize Mol. weight

Simulate NMR spectra (GODDESS)

Show Sweet-II 3D model Generate 3D coords by GLYCAM