1. Lipophilic Ga Complex with Broad-Spectrum Antimicrobial Activity and the Ability to Overcome Gallium Resistance in both Pseudomonas aeruginosa and Staphylococcus aureus .
- Author
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Wang Z, Li J, Benin BM, Yu B, Bunge SD, Abeydeera N, Huang SD, and Kim MH
- Subjects
- Anti-Bacterial Agents chemical synthesis, Anti-Bacterial Agents chemistry, Coordination Complexes chemical synthesis, Coordination Complexes chemistry, Dose-Response Relationship, Drug, Gallium chemistry, Molecular Structure, Structure-Activity Relationship, Anti-Bacterial Agents pharmacology, Coordination Complexes pharmacology, Drug Resistance, Bacterial drug effects, Gallium pharmacology, Pseudomonas aeruginosa drug effects, Staphylococcus aureus drug effects
- Abstract
Antibiotic resistance (AR) necessitates the discovery of new antimicrobials with alternative mechanisms of action to those employed by conventional antibiotics. One such strategy utilizes Ga
3+ to target iron metabolism, a critical process for survival. Still, Ga-based therapies are generally ineffective against Gram-positive bacteria and promote Ga resistance. In response to these drawbacks, we report a lipophilic Ga complex, [Ga2 L3 (bpy)2 ] (L = 2,2'-bis(3-hydroxy-1,4-naphthoquinone; bpy = 2,2'-bipyridine)), effective against drug-resistant Pseudomonas aeruginosa (DRPA; minimum inhibitory concentration, MIC = 10 μM = 14.8 μg/mL) and methicillin-resistant Staphylococcus aureus (MRSA, MIC = 100 μM = 148 μg/mL) without iron-limited conditions. Importantly, [Ga2 L3 (bpy)2 ] shows noticeably delayed and decreased resistance in both MRSA and DRPA, with only 8× MIC in DRPA and none in MRSA after 30 passages. This is likely due to the dual mode of action afforded by Ga (disruption of iron metabolism) and the ligand (reactive oxygen species production). Overall, [Ga2 L3 (bpy)2 ] demonstrates the utility of lipophilic metal complexes with multiple modes of action in combatting AR in Gram-positive and Gram-negative bacteria.- Published
- 2021
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