Dimethylglyoxime (DMG) is a nickel chelator with potential as an antimicrobial agent by inhibiting nickel-dependent enzymes in pathogens, offering novel therapeutic applications and strategies to combat bacterial, fungal, and protozoal infections, while addressing antibiotic resistance concerns.
Dimethylglyoxime (DMG)
Researched by:
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Karen Pendergrass
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Karen Pendergrass
Karen Pendergrass is a microbiome researcher specializing in microbiome-targeted interventions (MBTIs). She systematically analyzes scientific literature to identify microbial patterns, develop hypotheses, and validate interventions. As the founder of the Microbiome Signatures Database, she bridges microbiome research with clinical practice. In 2012, based on her own investigative research, she became the first documented case of FMT for Celiac Disease—four years before the first published case study.
Dimethylglyoxime (MG) is a chemical compound known for its ability to selectively chelate Nickel ions (Ni^2+), forming a bright red precipitate. This property has made MG a useful reagent in analytical chemistry for detecting and quantifying nickel. In fighting pathogens with nickel-dependent enzymes, such as those possessing urease or hydrogenase essential for their survival and […]
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Karen Pendergrass
Researched by:
-
Karen Pendergrass
ID
Karen Pendergrass
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
Overview Overview
Dimethylglyoxime (DMG) is a chemical compound known for its ability to selectively chelate Nickel ions (Ni^2+), forming a bright red precipitate. This property has made DMG a useful reagent in analytical chemistry for detecting and quantifying nickel. In fighting pathogens with nickel-dependent enzymes, such as those possessing urease or hydrogenase essential for their survival and pathogenicity, DMG or similar chelating agents could potentially serve as therapeutic agents by targeting and disrupting these nickel-dependent metabolic pathways.
Pathogen-inhibiting potential
Chelation of Nickel
Mechanism: DMG can bind to nickel ions, effectively sequestering them and preventing their incorporation into nickel-dependent enzymes. By chelating nickel, DMG deprives pathogens of the essential cofactor needed for the activity of critical enzymes like urease and hydrogenase.
Inhibition of Enzyme Activity
Urease: For bacteria like Helicobacter pylori, urease is vital for survival in acidic environments, such as the stomach. Urease converts urea into ammonia and carbon dioxide, which helps neutralize stomach acid. DMG-mediated nickel chelation would inhibit urease activity, compromising the bacterium’s ability to withstand acidic conditions.
Hydrogenase: Some bacteria use hydrogenase enzymes to oxidize hydrogen gas, which can be linked to energy production under certain conditions. By targeting nickel, DMG could disrupt hydrogen metabolism in these pathogens, affecting their energy conservation mechanisms.
Potential Therapeutic Applications
Selective Targeting: DMG’s selective chelation of nickel offers a targeted approach to inhibiting the growth of nickel-dependent pathogens without broadly affecting the host or beneficial microbiota that do not rely on nickel-dependent enzymes.
Combination Therapy: DMG could be combined with traditional antibiotics to enhance the effectiveness of treatment, particularly against resistant strains. By weakening the pathogens through enzyme inhibition, DMG might increase their susceptibility to antibiotics.
Considerations and Challenges
Specificity and Safety: While the concept of using DMG as an antimicrobial agent have shown significant promise, the specificity of DMG for nickel and its safety profile in humans would need careful evaluation. Ensuring that DMG does not adversely affect human cells or interfere with the metabolism of other essential micronutrients is crucial.
Delivery and Stability: Effective delivery mechanisms for DMG or similar chelating agents to the site of infection and ensuring stability and bioavailability are key challenges that need addressing for therapeutic use.
Research and Development: More research is required to understand the potential impacts of DMG on microbial communities and to develop effective and safe formulations for human use.
In summary, using dimethylglyoxime to fight against pathogens with nickel-dependent enzymes presents a novel antimicrobial strategy. By exploiting the essential role of nickel in these enzymes, DMG offers a potential pathway to develop targeted treatments against certain pathogens. However, extensive research is needed to explore its efficacy, safety, and application in clinical settings.
Nickel
Bacteria regulate transition metal levels through complex mechanisms to ensure survival and adaptability, influencing both their physiology and the development of antimicrobial strategies.
Nickel
Bacteria regulate transition metal levels through complex mechanisms to ensure survival and adaptability, influencing both their physiology and the development of antimicrobial strategies.