Targeting ADP-ribosylation as an Antimicrobial Strategy

Biochem Pharmacol. 2019 Sep;167:13-26. doi: 10.1016/j.bcp.2019.06.001. Epub 2019 Jun 6.

Abstract

ADP-ribosylation (ADPr) is an ancient reversible modification of cellular macromolecules controlling major biological processes as diverse as DNA damage repair, transcriptional regulation, intracellular transport, immune and stress responses, cell survival and proliferation. Furthermore, enzymatic reactions of ADPr are central in the pathogenesis of many human diseases, including infectious conditions. By providing a review of ADPr signalling in bacterial systems, we highlight the relevance of this chemical modification in the pathogenesis of human diseases depending on host-pathogen interactions. The post-antibiotic era has raised the need to find alternative approaches to antibiotic administration, as major pathogens becoming resistant to antibiotics. An in-depth understanding of ADPr reactions provides the rationale for designing novel antimicrobial strategies for treatment of infectious diseases. In addition, the understanding of mechanisms of ADPr by bacterial virulence factors offers important hints to improve our knowledge on cellular processes regulated by eukaryotic homologous enzymes, which are often involved in the pathogenesis of human diseases.

Keywords: ADP-ribosyl transferase (ART); ADP-ribosylation; ART bacterial toxins; Antimicrobial strategies; Poly(ADP-ribose) polymerase (PARP).

Publication types

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

MeSH terms

  • ADP-Ribosylation / drug effects*
  • ADP-Ribosylation / physiology
  • Animals
  • Anti-Infective Agents / metabolism
  • Anti-Infective Agents / pharmacology*
  • Drug Delivery Systems / methods*
  • Drug Delivery Systems / trends
  • Endotoxins / antagonists & inhibitors*
  • Endotoxins / metabolism
  • Humans
  • Signal Transduction / drug effects
  • Signal Transduction / physiology

Substances

  • Anti-Infective Agents
  • Endotoxins