Molecular mechanism of vSGLT inhibition by gneyulin reveals antiseptic properties against multidrug-resistant gram-negative bacteria

J Mol Model. 2019 Jun 11;25(7):186. doi: 10.1007/s00894-019-4073-9.

Abstract

Faced with the worldwide spread of multidrug-resistant (MDR) bacterial strains, together with a lack of any appropriate treatment, urgent steps to combat infectious diseases should be taken. Usually, bacterial components are studied to understand, by analogy, the functioning of human proteins. However, molecular data from bacteria gathered over the past decades provide a sound basis for the search for novel approaches in medical care. With this current work, we want to direct attention to inhibition of the vSGLT glucose transporter from Vibrio parahaemolyticus belonging to the sodium solute symporter (SSS) family, to block sugar transport into the bacterial cell and, as a consequence, to limit its growth. Potential bacteriostatic properties can be drawn from commercially available drugs developed for human diseases. This goal can also be reached with natural components from traditional herbal medicine. The presented data from the numerical analysis of 44 known inhibitors of sodium glucose symporters shed light on potential novel approaches in fighting Gram-negative multidrug-resistant microorganisms. Graphical abstract Molecular view on vSGLT channel inhibition by gneyulin B, the compound of natural origin.

Keywords: Aseptic agents; Bacterial resistance; Multidrug-resistant gram-negative microorganisms; vSGLT glucose transporter inhibition.

MeSH terms

  • Antisepsis / methods
  • Binding Sites
  • Drug Resistance, Multiple, Bacterial / drug effects
  • Gram-Negative Bacteria / drug effects
  • Humans
  • Ligands
  • Models, Molecular*
  • Protein Binding
  • Protein Conformation
  • Quantitative Structure-Activity Relationship*
  • Sodium-Glucose Transport Proteins / antagonists & inhibitors
  • Sodium-Glucose Transport Proteins / chemistry*
  • Stilbenes / chemistry*
  • Stilbenes / pharmacology
  • Vibrio parahaemolyticus / metabolism

Substances

  • Ligands
  • Sodium-Glucose Transport Proteins
  • Stilbenes
  • gneyulin B