Bacterial Polyphosphate Kinases Revisited: Role in Pathogenesis and Therapeutic Potential

Curr Drug Targets. 2019;20(3):292-301. doi: 10.2174/1389450119666180801120231.

Abstract

Bacterial infections have always been an unrestrained challenge to the medical community due to the rise of multi-drug tolerant and resistant strains. Pioneering work on Escherichia coli polyphosphate kinase (PPK) by Arthur Kornberg has generated great interest in this polyphosphate (PolyP) synthesizing enzyme. PPK has wide distribution among pathogens and is involved in promoting pathogenesis, stress management and susceptibility to antibiotics. Further, the absence of a PPK orthologue in humans makes it a potential drug target. This review covers the functional and structural aspects of polyphosphate kinases in bacterial pathogens. A description of molecules being designed against PPKs has been provided, challenges associated with PPK inhibitor design are highlighted and the strategies to enable development of efficient drug against this enzyme have also been discussed.

Keywords: PPK inhibitor; Pathogenesis; drug designing; stringent response; targeted inhibitor screening; virulence factors..

Publication types

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

MeSH terms

  • Animals
  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Bacteria / drug effects
  • Bacteria / enzymology
  • Bacteria / pathogenicity*
  • Bacterial Proteins / antagonists & inhibitors
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / metabolism
  • Drug Design
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Models, Molecular
  • Phosphotransferases (Alcohol Group Acceptor) / antagonists & inhibitors
  • Phosphotransferases (Alcohol Group Acceptor) / chemistry
  • Phosphotransferases (Alcohol Group Acceptor) / metabolism*
  • Phosphotransferases (Phosphate Group Acceptor)
  • Polyphosphates / metabolism
  • Structure-Activity Relationship

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Enzyme Inhibitors
  • Polyphosphates
  • Phosphotransferases (Alcohol Group Acceptor)
  • Phosphotransferases (Phosphate Group Acceptor)
  • polyphosphate kinase