Gallium as novel Antimicrobial Agents: Innovations in Combating Drug-Resistant Pathogens Original paper
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Metals
Metals
Heavy metals play a significant and multifaceted role in the pathogenicity of microbial species.
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Microbes
Microbes
Microbes, short for microorganisms, are tiny living organisms that are ubiquitous in the environment, including on and inside the human body. They play a crucial role in human health and disease, functioning within complex ecosystems in various parts of the body, such as the skin, mouth, gut, and respiratory tract. The human microbiome, which is […]
Microbiome Signatures identifies and validates condition-specific microbiome shifts and interventions to accelerate clinical translation. Our multidisciplinary team supports clinicians, researchers, and innovators in turning microbiome science into actionable medicine.
Karen Pendergrass
What was reviewed?
The study reviewed the advancements in the application of gallium-based compounds and gallium as novel 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?
The findings on gallium’s antimicrobial activity converge on its capacity to function as a redox-inert iron mimic that destabilizes iron-dependent metabolic pathways across diverse bacterial taxa. By substituting for ferric iron in essential enzymes and metabolic systems, gallium interrupts DNA synthesis, electron transport, oxidative stress responses, and biofilm maintenance. This mechanism provides broad-spectrum activity against multidrug-resistant organisms while minimizing the potential for resistance development. Advances in gallium delivery, including chelation strategies, nanomaterial-based carriers, doped bioglasses, and synergistic combinations with antibiotics, have markedly improved its solubility, bioavailability, and sustained antimicrobial performance, positioning gallium-based therapeutics as a promising class for addressing refractory and biofilm-associated infections.
| Major Findings | Summary of Evidence |
|---|---|
| Iron Mimicry and Enzyme Inactivation | Gallium substitutes for Fe³⁺ in iron-dependent enzymes, disrupting processes including ribonucleotide reductase-mediated DNA synthesis, electron transport, and oxidative stress regulation. Its redox-inert nature prevents enzymatic turnover, halting bacterial growth. |
| Disruption of Biofilms | Gallium impairs biofilm formation, particularly in Pseudomonas aeruginosa, by reducing iron availability required for biofilm stability and virulence expression. |
| Sustained-Release Delivery Systems | Gallium-doped bioglasses, alloys, and nanostructured carriers provide extended antimicrobial activity suitable for implant-related or chronic infections. |
| Bioavailability Enhancement | Chelation, ligand coordination, and nanocarriers overcome gallium hydrolysis in physiological environments, improving solubility and intracellular delivery. |
| Synergistic Antibacterial Strategies | Gallium works synergistically with antibiotics such as vancomycin and ciprofloxacin, restoring activity against resistant strains, lowering required doses, and reducing resistance emergence. |
| Nanotechnology Innovation | Liposomes, Janus micromotors, and other engineered nanomaterials improve targeting, biofilm penetration, and controlled release of gallium compounds for enhanced antimicrobial efficacy. |
What are the greatest implications of this review?
Gallium as a novel antimicrobial agent 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 such as low bioavailability and the need for targeted delivery necessitate further research. Nonetheless, its role as a complement to existing antibiotics could significantly delay the development of resistance and enhance antimicrobial strategies.
Citation
Li F, Liu F, Huang K, Yang S. Advancement of Gallium and Gallium-Based Compounds as Antimicrobial Agents. Front Bioeng Biotechnol. 2022 Feb 4;10:827960. doi: 10.3389/fbioe.2022.827960.
Gallium
Gallium is studied for its unique antimicrobial and anticancer properties. It inhibits metalloproteinases, disrupts bacterial iron metabolism, and may enhance antibiotic efficacy, particularly against resistant strains. Gallium compounds show potential as non-traditional therapeutic agents in treating infections and inhibiting cancer cell invasion and metastasis.
Gallium
Gallium is studied for its unique antimicrobial and anticancer properties. It inhibits metalloproteinases, disrupts bacterial iron metabolism, and may enhance antibiotic efficacy, particularly against resistant strains. Gallium compounds show potential as non-traditional therapeutic agents in treating infections and inhibiting cancer cell invasion and metastasis.