Identification and Characterization of a Metalloprotein Involved in Gallium Internalization in Pseudomonas aeruginosa

ACS Infect Dis. 2019 Oct 11;5(10):1693-1697. doi: 10.1021/acsinfecdis.9b00271. Epub 2019 Sep 5.

Abstract

Gallium nitrate (Ganite) is a potential drug for the treatment of Pseudomonas aeruginosa infection. CRISPR/Cas9-based gene mutagenesis studies reveal that siderophore pyochelin-facilitated uptake and an ABC transporter are two major Ga3+ internalization pathways in Pseudomonas aeruginosa (P. aeruginosa). Crystal structures reveal that Ga3+ and Fe3+ occupy exactly the same metal site of HitA, a periplasmic iron-binding protein of the ABC transporter system. The study provides a molecular basis for Ga3+ internalization by P. aeruginosa and facilitates gallium-based antimicrobial drug development.

Keywords: Pseudomonas aeruginosa; gallium nitrate; internalization pathway; iron metabolism; metalloprotein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP-Binding Cassette Transporters
  • Anti-Bacterial Agents / chemistry*
  • Anti-Bacterial Agents / metabolism*
  • Anti-Bacterial Agents / pharmacology
  • Drug Development
  • Gallium / metabolism*
  • Iron / metabolism
  • Metalloproteins / chemistry*
  • Metalloproteins / metabolism*
  • Metalloproteins / pharmacology
  • Models, Molecular
  • Mutagenesis
  • Periplasm / metabolism
  • Protein Conformation
  • Pseudomonas Infections / drug therapy
  • Pseudomonas aeruginosa / drug effects
  • Pseudomonas aeruginosa / metabolism*
  • Siderophores / genetics
  • Siderophores / metabolism

Substances

  • ATP-Binding Cassette Transporters
  • Anti-Bacterial Agents
  • Metalloproteins
  • Siderophores
  • Gallium
  • Iron
  • gallium nitrate