Genetic and Biochemical Mechanisms for Bacterial Lipid A Modifiers Associated with Polymyxin Resistance

Trends Biochem Sci. 2019 Nov;44(11):973-988. doi: 10.1016/j.tibs.2019.06.002. Epub 2019 Jul 3.

Abstract

Polymyxins are a group of detergent-like antimicrobial peptides that are the ultimate line of defense against carbapenem-resistant pathogens in clinical settings. Polymyxin resistance primarily originates from structural remodeling of lipid A anchored on bacterial surfaces. We integrate genetic, structural, and biochemical aspects of three major types of lipid A modifiers that have been shown to confer intrinsic colistin resistance. Namely, we highlight ArnT, a glycosyltransferase, EptA, a phosphoethanolamine transferase, and the AlmEFG tripartite system, which is restricted to EI Tor biotype of Vibrio cholerae O1. We also discuss the growing family of mobile colistin resistance (MCR) enzymes, each of which is analogous to EptA, and which pose great challenges to global public health.

Keywords: AlmEFG; ArnT; EptA; MCR; lipid A modifier; polymyxin resistance.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Anti-Bacterial Agents / chemistry*
  • Anti-Bacterial Agents / pharmacology
  • Bacterial Proteins / chemistry
  • Drug Resistance, Bacterial
  • Ethanolamines / metabolism
  • Gene Expression Regulation, Bacterial
  • Glycosyltransferases / metabolism
  • Humans
  • Lipid A / metabolism*
  • Models, Molecular
  • Phosphotransferases / metabolism
  • Polymyxins / chemistry*
  • Polymyxins / pharmacology
  • Protein Binding
  • Protein Conformation

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Ethanolamines
  • Lipid A
  • Polymyxins
  • phosphorylethanolamine
  • Glycosyltransferases
  • Phosphotransferases