Gallium Antimicrobial Agents: Innovations in Combating Drug-Resistant Pathogens Original paper

What was reviewed?

The study reviewed the advancements in the application of gallium and gallium-based compounds as antimicrobial agents. The review aimed to address the challenges of antimicrobial resistance (AMR) by highlighting gallium’s unique properties, mechanisms of action, and its potential as a non-antibiotic antibacterial strategy. The review summarized optimization strategies for gallium compounds, such as improving bioavailability and achieving sustained release, alongside synergistic effects with other antimicrobial agents.

Who was reviewed?

The review focused on multidrug-resistant (MDR) pathogens, including Pseudomonas aeruginosa, Mycobacterium tuberculosis, Acinetobacter baumannii, and methicillin-resistant Staphylococcus aureus (MRSA). It also discussed broader applications against Gram-positive and Gram-negative bacteria.

What were the most important findings?

Gallium mimics iron, a vital nutrient for bacterial growth, disrupting iron metabolism by substituting in iron-dependent processes. This “Trojan horse” mechanism inhibits bacterial proliferation by inactivating critical enzymes like ribonucleotide reductase and preventing biofilm formation, a significant defense strategy for bacteria. Key findings include:

Sustained-release systems, such as gallium-doped bioglasses and alloys, provide long-term antibacterial effects suitable for implant-related infections.

Gallium is redox-inert and disrupts bacterial metabolism by replacing iron, thereby impairing DNA synthesis, electron transport, and oxidative stress responses.

Gallium-based compounds have enhanced their solubility and antibacterial efficacy through chelation and nanomaterial delivery systems.

Synergistic strategies, combining gallium with antibiotics or antimicrobial agents, restore the efficacy of resistant antibiotics, reduce required dosages, and mitigate resistance development.

Gallium acts as a redox-inert iron mimic, disrupting bacterial iron-dependent metabolic pathways and enzyme functions, such as ribonucleotide reductase, critical for DNA synthesis. This mechanism renders it effective against MDR pathogens while minimizing bacterial resistance development. Key findings include:

Bioavailability Challenges: Gallium compounds face hydrolysis in physiological conditions, limiting their effectiveness. Strategies like coordination with ligands, incorporation into nanomaterials, and use of gallium-doped bioglasses have significantly enhanced bioavailability and sustained release.

Synergistic Antibacterial Effects: Gallium combined with antibiotics (e.g., ciprofloxacin, vancomycin) restores antibiotic efficacy against resistant strains and enhances their potency. Additionally, gallium complexes combined with metal ions or photodynamic therapies show amplified antibacterial effects.

Biofilm Disruption: Gallium can inhibit biofilm formation, a major resistance mechanism, particularly in Pseudomonas aeruginosa, by reducing iron availability needed for biofilm maintenance.

Nanotechnology Advances: Gallium-loaded nanomaterials, such as liposomes and Janus micromotors, improve targeting and sustained release, offering a promising avenue for clinical applications.

What are the greatest implications of this review?

Gallium represents a promising alternative to traditional antibiotics, especially against MDR pathogens. The review highlights potential clinical applications in treating implant-related infections, respiratory conditions, and other systemic infections. However, limitations like low bioavailability and the need for targeted delivery require further research. Nonetheless, its role as a complement to existing antibiotics could significantly delay resistance development and enhance antimicrobial strategies.