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
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Research Support, Non-U.S. Gov't
MeSH terms
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ATP-Binding Cassette Transporters
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Anti-Bacterial Agents / chemistry*
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Anti-Bacterial Agents / metabolism*
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Anti-Bacterial Agents / pharmacology
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Drug Development
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Gallium / metabolism*
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Iron / metabolism
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Metalloproteins / chemistry*
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Metalloproteins / metabolism*
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Metalloproteins / pharmacology
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Models, Molecular
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Mutagenesis
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Periplasm / metabolism
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Protein Conformation
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Pseudomonas Infections / drug therapy
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Pseudomonas aeruginosa / drug effects
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Pseudomonas aeruginosa / metabolism*
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Siderophores / genetics
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Siderophores / metabolism
Substances
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ATP-Binding Cassette Transporters
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Anti-Bacterial Agents
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Metalloproteins
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Siderophores
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Gallium
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Iron
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gallium nitrate