Sortase A (SrtA) inhibitors as an alternative treatment for superbug infections

Drug Discov Today. 2021 Sep;26(9):2164-2172. doi: 10.1016/j.drudis.2021.03.019. Epub 2021 Mar 27.

Abstract

Virulence factor, sortase A (SrtA), has crucial roles in the pathogenesis of Gram-positive superbugs. SrtA is a bacterial cell membrane enzyme that anchors crucial virulence factors to the cell wall surface of Gram-positive bacteria. SrtA is not necessary for bacterial growth and viability and is conveniently accessible in the cell membrane; therefore, it is an ideal target for antivirulence drug development. In this review, we focus on antimicrobial resistance (AMR)-expressing bacteria and SrtA as a potential target for overcoming AMR. The mechanism of action of SrtA and its inhibition by various types of inhibitors, such as synthetic small molecules, peptides, and natural products, are provided. Future SrtA research perspectives for alternative drug development to antibiotics are also proposed.

Keywords: Anti-virulence therapy; Antimicrobial resistance; Gram-positive bacteria; Sortase A inhibitors; Virulence factors.

Publication types

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

MeSH terms

  • Aminoacyltransferases / antagonists & inhibitors*
  • Aminoacyltransferases / chemistry
  • Aminoacyltransferases / metabolism
  • Animals
  • Anti-Bacterial Agents / therapeutic use
  • Bacterial Proteins / antagonists & inhibitors*
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / metabolism
  • Biological Products / therapeutic use
  • Cysteine Endopeptidases / chemistry
  • Cysteine Endopeptidases / metabolism
  • Drug Resistance, Bacterial*
  • Gram-Positive Bacterial Infections / drug therapy*
  • Humans
  • Peptides / therapeutic use

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Biological Products
  • Peptides
  • Aminoacyltransferases
  • sortase A
  • Cysteine Endopeptidases