Nickel in Escherichia coli: Metabolic and Pathogenic Roles
Researched by:
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Karen Pendergrass
ID
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.
Nickel plays a crucial role in Escherichia coli, serving as a cofactor for hydrogenases, urease, and detoxification enzymes. These functions support metabolism, acid resistance, and virulence in pathogenic strains like TEC. E. coli also employs specialized nickel acquisition systems to counteract host-imposed metal sequestration, ensuring enzymatic activity in hostile environments.
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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 
References Overview
Nickel is a critical cofactor in several enzymatic systems within Escherichia coli (E. coli), supporting metabolic adaptability, survival under stress, and, in pathogenic strains, virulence. Despite its significance, nickel availability is tightly regulated due to potential toxicity. Several nickel-dependent enzymes in E. coli illustrate the dual role of nickel in metabolism and pathogenesis, particularly through hydrogenases, urease (in specific strains), and detoxification enzymes. This short section provides a focused overview of the role of nickel in Escherichia coli, summarizing key findings from the broader review Role of Nickel in Microbial Pathogenesis by Maier and Benoit (2019). [1] While the original review comprehensively discusses nickel-dependent enzymes across multiple pathogens, this segment highlights E. coli-specific aspects, particularly its nickel-requiring enzymes, acquisition mechanisms, and their contributions to metabolism and pathogenicity. The following discussion synthesizes relevant data to illustrate nickel’s role in E. coli survival, adaptation, and virulence.
Nickel-Dependent Enzymes in E. coli
Among the major nickel-requiring enzymes in E. coli, the [NiFe] hydrogenases play a central role in anaerobic respiration. These include Hyd-1, Hyd-2, and Hyc (Hyd-3), all of which contribute to hydrogen metabolism. Hyd-1 and Hyd-2 are uptake-type hydrogenases involved in H₂ oxidation, contributing to energy production via proton motive force (PMF), while Hyc is a formate hydrogenlyase complex enzyme that facilitates H₂ evolution, crucial for pH homeostasis in fermentation conditions. Another key nickel-requiring enzyme is urease, present in certain pathogenic strains like Shiga toxin-producing E. coli (STEC). This enzyme hydrolyzes urea into ammonia and CO₂, a function that enables survival in acidic environments and enhances host colonization. The role of urease in E. coli parallels that in other urease-positive pathogens, contributing to nitrogen acquisition and pH regulation. Additional nickel-dependent enzymes include Ni-acireductone dioxygenase (ARD) and Ni-glyoxalase I (Glo-I), present in all gammaproteobacteria, which enhance metabolic flexibility and stress resistance. ARD participates in the methionine salvage pathway, supporting nutrient recycling, while Glo-I detoxifies methylglyoxal, a toxic glycolytic byproduct, thus preventing metabolic stress.
| Nickel-Dependent Enzyme | Function |
|---|---|
| Hyd-1, Hyd-2 (H₂-uptake) | Catalyze H₂ oxidation, generating energy via proton motive force (PMF). Support gut colonization and anaerobic survival. |
| Hyc (Hyd-3, FHL complex) | Facilitates H₂ evolution to dissipate acidity in fermentation, maintaining pH balance. Contributes to acid stress resistance. |
| Urease (STEC strains) | Hydrolyzes urea into ammonia and CO₂, neutralizing pH and providing nitrogen. Enhances host colonization in acidic environments. |
| Ni-ARD | Participates in methionine salvage, supporting metabolic flexibility. Aids E. coli adaptation to varying host environments. |
| Ni-Glo-I | Detoxifies methylglyoxal, preventing glycolytic stress. Maintains cellular homeostasis, supporting survival under metabolic stress. |
Nickel Acquisition in E. coli
Nickel uptake in E. coli is facilitated primarily through the NikABCDE transporter, an ATP-binding cassette (ABC) system that recognizes Ni-(L-His)₂ complexes and ensures sufficient nickel supply for enzymatic activity. In uropathogenic E. coli (UPEC), an additional mechanism involves the yersiniabactin metallophore system, which aids in nickel acquisition under host-imposed metal sequestration conditions (nutritional immunity). These uptake strategies underscore nickel’s importance in bacterial persistence, particularly in host environments where metal availability is restricted.
Functional Relevance in Pathogenesis
While E. coli is often a commensal organism, nickel utilization plays a crucial role in pathogenic strains. Hydrogenases facilitate anaerobic growth in the gut, urease enhances colonization in STEC, and nickel acquisition systems help counteract host immune strategies aimed at limiting bacterial proliferation. The ability to maintain nickel homeostasis enables E. coli to thrive in diverse and often hostile environments, reinforcing the necessity of nickel-dependent enzymes for both metabolic efficiency and pathogenic potential.
References
- Role of Nickel in Microbial Pathogenesis.. Maier RJ, Benoit SL.. (Inorganics. 2019; 7(7):80.)