DNA replication proteins as potential targets for antimicrobials in drug-resistant bacterial pathogens

J Antimicrob Chemother. 2017 May 1;72(5):1275-1284. doi: 10.1093/jac/dkw548.

Abstract

With the impending crisis of antimicrobial resistance, there is an urgent need to develop novel antimicrobials to combat difficult infections and MDR pathogenic microorganisms. DNA replication is essential for cell viability and is therefore an attractive target for antimicrobials. Although several antimicrobials targeting DNA replication proteins have been developed to date, gyrase/topoisomerase inhibitors are the only class widely used in the clinic. Given the numerous essential proteins in the bacterial replisome that may serve as a potential target for inhibitors and the relative paucity of suitable compounds, it is evident that antimicrobials targeting the replisome are underdeveloped so far. In this review, we report on the diversity of antimicrobial compounds targeting DNA replication and highlight some of the challenges in developing new drugs that target this process.

Publication types

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

MeSH terms

  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Anti-Bacterial Agents / therapeutic use
  • Bacteria / drug effects*
  • Bacteria / metabolism
  • Bacteria / pathogenicity
  • Bacterial Proteins / antagonists & inhibitors*
  • DNA Replication / drug effects*
  • Drug Design*
  • Drug Resistance, Multiple, Bacterial*
  • Humans
  • Topoisomerase II Inhibitors / chemistry
  • Topoisomerase II Inhibitors / pharmacology
  • Topoisomerase II Inhibitors / therapeutic use

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Topoisomerase II Inhibitors