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Dimethylglyoxime (DMG) majorpublished
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:
-
Karen Pendergrass
Karen Pendergrass
Read MoreKaren 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 represents a novel therapeutic paradigm that exploits a fundamental metabolic difference between pathogenic bacteria and their mammalian hosts. By selectively depleting bacterial access to nickel, a cofactor essential for multiple pathogenic enzymes but unnecessary for human physiology, DMG offers a theoretically host-sparing antimicrobial approach.
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Karen Pendergrass
Read More
Researched by:
-
Karen Pendergrass
Karen Pendergrass
Read More
Page Snapshot
Microbiome-targeted interventions (MBTIs) are validated using a dual-evidence logical framework. First, the intervention must realign the condition’s microbiome signature by increasing beneficial taxa that are consistently depleted and reducing pathogenic taxa that are consistently enriched. Second, the intervention must demonstrate measurable clinical benefit. Concordance of these effects in the same context validates the intervention as an MBTI and supports the clinical relevance of the microbiome signature.
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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
Dimethylglyoxime (DMG) is a nickel-specific chelator compound that has been utilized for decades in various environmental and analytical applications. While traditionally employed for detecting, quantifying, or reducing nickel levels in diverse environmental contexts, recent research has revealed its potential as a therapeutic agent targeting pathogenic bacteria and their nickel-dependent metabolic functions.[1]
Mechanism of Action
The application of DMG as a microbiome-targeted intervention (MBTI) is based on a sophisticated understanding of bacterial metabolism and the essential role of nickel as a bacterial cofactor. Many enteric bacteria require nickel as a critical cofactor for several essential enzymatic functions.[2] [3] Specifically, nickel is needed for enzymes including acireductone dioxygenase, β-hydrogenase, glyoxalase I, superoxide dismutase (SOD), and urease.[4] This metabolic dependency on nickel presents a unique therapeutic opportunity, as mammalian hosts do not require nickel for any known enzymatic processes. Therefore, targeting nickel availability to pathogens represents a selective antimicrobial strategy that does not harm host metabolism. The nickel-chelation approach has gained attention because of the necessity of these nickel-dependent enzymes for pathogen virulence and survival. For instance, nickel-containing hydrogenases are essential for bacterial colonization and persistence within host tissues.[5] Similarly, urease, another critical nickel-dependent enzyme, plays dual roles in pathogenesis by facilitating survival in acidic environments and providing essential nitrogen sources for bacterial growth.[6] By depleting bacterial access to bioavailable nickel through DMG-mediated chelation, researchers theorized that bacterial growth and virulence could be significantly attenuated.
Dimethylglyoxime (DMG) and Multi-Drug Resistant Pathogens
The potential clinical significance of DMG as an antimicrobial therapy is underscored by the prevalence of multidrug-resistant (MDR) enteric pathogens and their impact on public health. The World Health Organization (WHO) has identified carbapenem-resistant Enterobacteriaceae (CRE) in its highest priority category for urgent antimicrobial development.[7] Of particular relevance to DMG as a therapeutic approach is that among the twelve MDR pathogens identified on the WHO priority list, ten are nickel-dependent urease-positive, six possess nickel-dependent hydrogenase activity, and four possess both enzyme systems.[8] Furthermore, eight of these MDR species contain the nickel-dependent glyoxalase I enzyme, and five contain the nickel-dependent acireductone dioxygenase.[9] This widespread prevalence of nickel-dependent enzymes among the most concerning MDR pathogens suggests that DMG-mediated nickel chelation could provide broad-spectrum activity against multiple priority pathogens simultaneously by targeting multiple essential nickel-requiring enzymes.[10]
Conclusions and Future Perspective
Dimethylglyoxime (DMG) represents a novel therapeutic paradigm that exploits a fundamental metabolic difference between pathogenic bacteria and their mammalian hosts. By selectively depleting bacterial access to nickel, a cofactor essential for multiple pathogenic enzymes but unnecessary for human physiology, DMG offers a host-sparing antimicrobial approach. The compelling in vitro and in vivo evidence demonstrating efficacy against multidrug-resistant enteric pathogens, combined with a favorable safety profile in both mammalian and invertebrate models, suggests that DMG-mediated nickel-chelation therapy deserves further investigation as a microbiome-targeted intervention (MBTI) for combating recalcitrant bacterial infections. [11]
Frequently Asked Questions
What is Dimethylglyoxime (DMG)?
Quick answer: Dimethylglyoxime (DMG) is a nickel-specific chelator compound that has been utilized for decades in various environmental and analytical applications. While traditionally employed for detecting, quantifying, or reducing nickel levels in diverse environmental contexts, recent research has revealed its potential as a therapeutic agent targeting pathogenic bacteria and their nickel-dependent metabolic functions.[1]
Research Feed
Nickel chelation therapy as an approach to combat multi-drug resistant enteric pathogens
September 25, 2019
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Metals •
Metals
Heavy metals influence microbial pathogenicity in two ways: they can be toxic to microbes by disrupting cellular functions and inducing oxidative stress, and they can be exploited by pathogens to enhance survival, resist treatment, and evade immunity. Understanding metal–microbe interactions supports better antimicrobial and public health strategies.
Alias iure reprehenderit aut accusantium. Molestiae dolore suscipit. Necessitatibus eum quaerat. Repudiandae suscipit quo necessitatibus. Voluptatibus ullam nulla temporibus nobis. Atque eaque sed totam est assumenda. Porro modi soluta consequuntur veritatis excepturi minus delectus reprehenderit est. Eveniet labore ut quas minima aliquid quibusdam. Vitae possimus fuga praesentium eveniet debitis exercitationem deleniti.
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Role of Nickel in Microbial Pathogenesis
May 21, 2019
/
Metals •
Metals
Heavy metals influence microbial pathogenicity in two ways: they can be toxic to microbes by disrupting cellular functions and inducing oxidative stress, and they can be exploited by pathogens to enhance survival, resist treatment, and evade immunity. Understanding metal–microbe interactions supports better antimicrobial and public health strategies.
Alias iure reprehenderit aut accusantium. Molestiae dolore suscipit. Necessitatibus eum quaerat. Repudiandae suscipit quo necessitatibus. Voluptatibus ullam nulla temporibus nobis. Atque eaque sed totam est assumenda. Porro modi soluta consequuntur veritatis excepturi minus delectus reprehenderit est. Eveniet labore ut quas minima aliquid quibusdam. Vitae possimus fuga praesentium eveniet debitis exercitationem deleniti.
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Nickel chelator dimethylglyoxime inhibits amyloid beta aggregation in vitro and targets nickel-driven Alzheimer’s mechanisms
Dimethylglyoxime (DMG) •
Dimethylglyoxime (DMG)
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.
Nickel •
Nickel
Did you know?
Nickel is essential for the virulence of many pathogens, but not a single human enzyme requires it. This makes nickel metabolism a unique microbial vulnerability and a promising antimicrobial target.
Alias iure reprehenderit aut accusantium. Molestiae dolore suscipit. Necessitatibus eum quaerat. Repudiandae suscipit quo necessitatibus. Voluptatibus ullam nulla temporibus nobis. Atque eaque sed totam est assumenda. Porro modi soluta consequuntur veritatis excepturi minus delectus reprehenderit est. Eveniet labore ut quas minima aliquid quibusdam. Vitae possimus fuga praesentium eveniet debitis exercitationem deleniti.
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Ni(II) Cd(II) mixed ligand complexes as dual antimicrobial and anti inflammatory agents
Dimethylglyoxime (DMG) •
Dimethylglyoxime (DMG)
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.
Nickel •
Nickel
Did you know?
Nickel is essential for the virulence of many pathogens, but not a single human enzyme requires it. This makes nickel metabolism a unique microbial vulnerability and a promising antimicrobial target.
Cadmium (Cd) •
Cadmium (Cd)
Cadmium poses significant environmental and health risks, especially due to its persistence in the ecosystem. Unlike some other metals, cadmium does not degrade and can accumulate over time in soil and water, posing a threat to both ecosystems and human health. Industries that process or manufacture batteries, pigments, and plastics are major sources of cadmium pollution.
Alias iure reprehenderit aut accusantium. Molestiae dolore suscipit. Necessitatibus eum quaerat. Repudiandae suscipit quo necessitatibus. Voluptatibus ullam nulla temporibus nobis. Atque eaque sed totam est assumenda. Porro modi soluta consequuntur veritatis excepturi minus delectus reprehenderit est. Eveniet labore ut quas minima aliquid quibusdam. Vitae possimus fuga praesentium eveniet debitis exercitationem deleniti.
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Nickel chelators and urease inhibition in Klebsiella pneumoniae and bacterial nickel transport
Urease •
Urease
Did you know?
Urease is an enzyme made by microbes, and its ammonia production can either protect against cavities or trigger kidney stones.
Alias iure reprehenderit aut accusantium. Molestiae dolore suscipit. Necessitatibus eum quaerat. Repudiandae suscipit quo necessitatibus. Voluptatibus ullam nulla temporibus nobis. Atque eaque sed totam est assumenda. Porro modi soluta consequuntur veritatis excepturi minus delectus reprehenderit est. Eveniet labore ut quas minima aliquid quibusdam. Vitae possimus fuga praesentium eveniet debitis exercitationem deleniti.
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Update History
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.
Microbiome-Targeted Interventions (MBTIs)
Microbiome Targeted Interventions (MBTIs) are cutting-edge treatments that utilize information from Microbiome Signatures to modulate the microbiome, revolutionizing medicine with unparalleled precision and impact.
Urease
Urease is a nickel-dependent microbial enzyme that breaks down urea into ammonia, altering local pH and nitrogen availability. While essential for microbial survival in acidic niches and nutrient-limited environments, urease activity also contributes to conditions like ulcers, urinary stones, colitis, and hepatic encephalopathy.
Nickel
Bacteria regulate transition metal levels through complex mechanisms to ensure survival and adaptability, influencing both their physiology and the development of antimicrobial strategies.
Urease
Urease is a nickel-dependent microbial enzyme that breaks down urea into ammonia, altering local pH and nitrogen availability. While essential for microbial survival in acidic niches and nutrient-limited environments, urease activity also contributes to conditions like ulcers, urinary stones, colitis, and hepatic encephalopathy.
Nickel
Bacteria regulate transition metal levels through complex mechanisms to ensure survival and adaptability, influencing both their physiology and the development of antimicrobial strategies.
Urease
Urease is a nickel-dependent microbial enzyme that breaks down urea into ammonia, altering local pH and nitrogen availability. While essential for microbial survival in acidic niches and nutrient-limited environments, urease activity also contributes to conditions like ulcers, urinary stones, colitis, and hepatic encephalopathy.
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.
Microbiome-Targeted Interventions (MBTIs)
Microbiome Targeted Interventions (MBTIs) are cutting-edge treatments that utilize information from Microbiome Signatures to modulate the microbiome, revolutionizing medicine with unparalleled precision and impact.
Metals
Heavy metals influence microbial pathogenicity in two ways: they can be toxic to microbes by disrupting cellular functions and inducing oxidative stress, and they can be exploited by pathogens to enhance survival, resist treatment, and evade immunity. Understanding metal–microbe interactions supports better antimicrobial and public health strategies.
Metals
Heavy metals influence microbial pathogenicity in two ways: they can be toxic to microbes by disrupting cellular functions and inducing oxidative stress, and they can be exploited by pathogens to enhance survival, resist treatment, and evade immunity. Understanding metal–microbe interactions supports better antimicrobial and public health strategies.
Dimethylglyoxime (DMG)
Dimethylglyoxime represents a novel therapeutic paradigm that exploits a fundamental metabolic difference between pathogenic bacteria and their mammalian hosts. By selectively depleting bacterial access to nickel, a cofactor essential for multiple pathogenic enzymes but unnecessary for human physiology, DMG offers a theoretically host-sparing antimicrobial approach.
Nickel
Bacteria regulate transition metal levels through complex mechanisms to ensure survival and adaptability, influencing both their physiology and the development of antimicrobial strategies.
Dimethylglyoxime (DMG)
Dimethylglyoxime represents a novel therapeutic paradigm that exploits a fundamental metabolic difference between pathogenic bacteria and their mammalian hosts. By selectively depleting bacterial access to nickel, a cofactor essential for multiple pathogenic enzymes but unnecessary for human physiology, DMG offers a theoretically host-sparing antimicrobial approach.
Nickel
Bacteria regulate transition metal levels through complex mechanisms to ensure survival and adaptability, influencing both their physiology and the development of antimicrobial strategies.
Cadmium (Cd)
Cadmium (Cd) is a highly toxic heavy metal commonly found in industrial, agricultural, and environmental settings. Exposure to cadmium can occur through contaminated water, food, soil, and air, and it has been linked to a variety of health issues, including kidney damage, osteoporosis, and cancer. In agriculture, cadmium is often present in phosphate fertilizers and can accumulate in plants, entering the food chain. Its toxicity to living organisms makes cadmium a subject of regulatory concern worldwide, particularly in industrial waste disposal and environmental monitoring.
Urease
Urease is a nickel-dependent microbial enzyme that breaks down urea into ammonia, altering local pH and nitrogen availability. While essential for microbial survival in acidic niches and nutrient-limited environments, urease activity also contributes to conditions like ulcers, urinary stones, colitis, and hepatic encephalopathy.
References
- Nickel chelation therapy as an approach to combat multi-drug resistant enteric pathogens.. Benoit SL, Schmalstig AA, Glushka J, Maier SE, Edison AS, Maier RJ.. (Scientific Reports. 2019)
- Nickel chelation therapy as an approach to combat multi-drug resistant enteric pathogens.. Benoit SL, Schmalstig AA, Glushka J, Maier SE, Edison AS, Maier RJ.. (Scientific Reports. 2019)
- Role of Nickel in Microbial Pathogenesis.. Maier, R. J., & Benoit, S. L.. (Inorganics. 2019; 7(7):80.)
- Role of Nickel in Microbial Pathogenesis.. Maier, R. J., & Benoit, S. L.. (Inorganics. 2019; 7(7):80.)
- Role of Nickel in Microbial Pathogenesis.. Maier, R. J., & Benoit, S. L.. (Inorganics. 2019; 7(7):80.)
- Role of Nickel in Microbial Pathogenesis.. Maier, R. J., & Benoit, S. L.. (Inorganics. 2019; 7(7):80.)
- Nickel chelation therapy as an approach to combat multi-drug resistant enteric pathogens.. Benoit SL, Schmalstig AA, Glushka J, Maier SE, Edison AS, Maier RJ.. (Scientific Reports. 2019)
- Nickel chelation therapy as an approach to combat multi-drug resistant enteric pathogens.. Benoit SL, Schmalstig AA, Glushka J, Maier SE, Edison AS, Maier RJ.. (Scientific Reports. 2019)
- Nickel chelation therapy as an approach to combat multi-drug resistant enteric pathogens.. Benoit SL, Schmalstig AA, Glushka J, Maier SE, Edison AS, Maier RJ.. (Scientific Reports. 2019)
- Nickel chelation therapy as an approach to combat multi-drug resistant enteric pathogens.. Benoit SL, Schmalstig AA, Glushka J, Maier SE, Edison AS, Maier RJ.. (Scientific Reports. 2019)
- Nickel chelation therapy as an approach to combat multi-drug resistant enteric pathogens.. Benoit SL, Schmalstig AA, Glushka J, Maier SE, Edison AS, Maier RJ.. (Scientific Reports. 2019)
Benoit SL, Schmalstig AA, Glushka J, Maier SE, Edison AS, Maier RJ.
Nickel chelation therapy as an approach to combat multi-drug resistant enteric pathogens.Scientific Reports. 2019
Read ReviewBenoit SL, Schmalstig AA, Glushka J, Maier SE, Edison AS, Maier RJ.
Nickel chelation therapy as an approach to combat multi-drug resistant enteric pathogens.Scientific Reports. 2019
Read ReviewMaier, R. J., & Benoit, S. L.
Role of Nickel in Microbial Pathogenesis.Inorganics. 2019; 7(7):80.
Read ReviewMaier, R. J., & Benoit, S. L.
Role of Nickel in Microbial Pathogenesis.Inorganics. 2019; 7(7):80.
Read ReviewMaier, R. J., & Benoit, S. L.
Role of Nickel in Microbial Pathogenesis.Inorganics. 2019; 7(7):80.
Read ReviewMaier, R. J., & Benoit, S. L.
Role of Nickel in Microbial Pathogenesis.Inorganics. 2019; 7(7):80.
Read ReviewBenoit SL, Schmalstig AA, Glushka J, Maier SE, Edison AS, Maier RJ.
Nickel chelation therapy as an approach to combat multi-drug resistant enteric pathogens.Scientific Reports. 2019
Read ReviewBenoit SL, Schmalstig AA, Glushka J, Maier SE, Edison AS, Maier RJ.
Nickel chelation therapy as an approach to combat multi-drug resistant enteric pathogens.Scientific Reports. 2019
Read ReviewBenoit SL, Schmalstig AA, Glushka J, Maier SE, Edison AS, Maier RJ.
Nickel chelation therapy as an approach to combat multi-drug resistant enteric pathogens.Scientific Reports. 2019
Read ReviewBenoit SL, Schmalstig AA, Glushka J, Maier SE, Edison AS, Maier RJ.
Nickel chelation therapy as an approach to combat multi-drug resistant enteric pathogens.Scientific Reports. 2019
Read ReviewBenoit SL, Schmalstig AA, Glushka J, Maier SE, Edison AS, Maier RJ.
Nickel chelation therapy as an approach to combat multi-drug resistant enteric pathogens.Scientific Reports. 2019
Read Review