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

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.