Aerobactin Synthesis Proteins as Antivirulence Targets in Hypervirulent Klebsiella pneumoniae

ACS Infect Dis. 2019 Jul 12;5(7):1052-1054. doi: 10.1021/acsinfecdis.9b00117. Epub 2019 Apr 29.

Abstract

Hypervirulent Klebsiella pneumoniae (hvKp) is an underrecognized pathotype of K. pneumoniae since the majority of cases have occurred in East Asia. However, hvKp is a public health threat due to its ability to infect healthy individuals, ongoing dissemination, and acquisition of resistance determinants. hvKp-directed antivirulence therapy is appealing since it has the potential to minimize resistance selection. The discovery that aerobactin is a critical hvKp-specific virulence factor has made its biosynthetic enzymes attractive targets for the development of small molecule inhibitors. However, identification of additional high value targets is needed to enable a robust countermeasure program for this evolving superbug.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / metabolism
  • Biosynthetic Pathways / drug effects*
  • Drug Development
  • Drug Resistance, Bacterial / drug effects
  • Gene Expression Regulation, Bacterial / drug effects
  • Humans
  • Hydroxamic Acids / metabolism*
  • Klebsiella pneumoniae / drug effects
  • Klebsiella pneumoniae / metabolism
  • Klebsiella pneumoniae / pathogenicity*
  • Models, Molecular
  • Small Molecule Libraries / pharmacology*
  • Virulence / drug effects

Substances

  • Bacterial Proteins
  • Hydroxamic Acids
  • Small Molecule Libraries
  • aerobactin