FtsZ as an Antibacterial Target: Status and Guidelines for Progressing This Avenue

ACS Infect Dis. 2019 Aug 9;5(8):1279-1294. doi: 10.1021/acsinfecdis.9b00055. Epub 2019 Jul 17.

Abstract

The disturbing increase in the number of bacterial pathogens that are resistant to multiple, or sometimes all, current antibiotics highlights the desperate need to pursue the discovery and development of novel classes of antibacterials. The wealth of knowledge available about the bacterial cell division machinery has aided target-driven approaches to identify new inhibitor compounds. The main division target being pursued is the highly conserved and essential protein FtsZ. Despite very active research on FtsZ inhibitors for several years, this protein is not yet targeted by any commercial antibiotic. Here, we discuss the suitability of FtsZ as an antibacterial target for drug development and review progress achieved in this area. We use hindsight to highlight the gaps that have slowed progress in FtsZ inhibitor development and to suggest guidelines for concluding that FtsZ is actually the target of these molecules, a key missing link in several studies. In moving forward, a multidisciplinary, communicative, and collaborative process, with sharing of research expertise, is critical if we are to succeed.

Keywords: FtsZ; antimicrobial resistance; bacterial cell division; drug discovery; transdisciplinary research.

Publication types

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

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Bacteria / chemistry
  • Bacteria / drug effects*
  • Bacterial Proteins / antagonists & inhibitors*
  • Bacterial Proteins / chemistry*
  • Cell Division
  • Clinical Trials as Topic
  • Cytoskeletal Proteins / antagonists & inhibitors*
  • Cytoskeletal Proteins / chemistry*
  • Drug Discovery
  • Humans
  • Research

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Cytoskeletal Proteins
  • FtsZ protein, Bacteria