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Microbes & Immunity Copper and cuproptosis in immunity

targets. 69,70 The detection of these biomarkers altogether can aid hinder the process of bacterial copper transport, restricting
in further understanding disease mechanisms and developing the uptake or efflux of copper ions and thus disturbing
personalized treatment strategies. the normal copper homeostasis within the bacteria; (iv)
Copper-related genes and key molecules in the cuproptosis creating inhibitors that target the copper-binding protein
pathway can serve as targets for novel drug development, where CopZ. By disrupting the interaction between CopZ and
inhibitors or activators targeting specific genes or signaling copper, the bacteria’s ability to bind and sequester copper is
compromised, leading to abnormal copper metabolism; (v)
pathways can modulate copper metabolism. For example, developing inhibitors against the copper-resistance protein
inhibiting certain copper transport proteins may help restrict CopY. This can impede the bacteria’s overall copper resistance
tumor growth. Research has established a cuproptosis-related function, making them more vulnerable to the toxic effects
gene signature that can effectively predict the prognosis of of copper in the environment. The importance of copper in
hepatocellular carcinoma patients, revealing that upregulation human physiological and pathological processes—especially
of pyridoxal kinase promotes the proliferation and metastasis in maintaining immune function, lipid balance, and related
of liver cancer, whereas PDXK deficiency enhances the diseases such as ischemic heart disease and non-alcoholic
sensitivity of liver cancer cells to cuproptosis inducers, fatty liver disease —necessitates further exploration of
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indicating that PDXK may be a potential diagnostic and biomarkers for copper deficiency, dietary recommendations,
therapeutic target for liver cancer. Bioinformatics analysis and its potential impacts on health.
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has identified the significant role of copper metabolism-
related genes (CMRGs) in osteosarcoma patient prognosis, 8. Summary and future direction
immune microenvironment, and drug sensitivity, shedding
light on the potential relationship between copper metabolism Copper homeostasis and cuproptosis are correlated with
and osteosarcoma and suggesting that CMRGs could serve tuberculosis. The cellular metabolic process of cuproptosis
as novel prognostic markers and therapeutic targets. mainly disrupts the tricarboxylic acid cycle and may
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Furthermore, therapeutic approaches based on copper-based play a regulatory role in the progression of tuberculosis.
drugs or copper supplementation have shown potential in Cuproptosis is a newly discovered form of regulatory cell
anticancer strategies and immunomodulation. These studies death that is closely related to other forms of regulated
present new opportunities for the clinical application of cell death, suggesting a potential relationship between
copper-related biology. cuproptosis and tuberculosis. Many researchers are now
Utilizing bacterial cuproptosis mechanisms can lead investigating this relationship with various major diseases.
to the development of novel antibacterial measures. At present, despite existing clinical options, there are no
effective treatments for tuberculosis. Treatment efficacy
A nano-drug, nitrite-oxidizing nanoparticles embedded in varies among patients due to different factors. Researchers are
electrodeposited copper (NP@ESCu), combined with copper beginning to explore the link between copper dysregulation
and elesclomol, has been designed to induce cuproptosis in and tuberculosis. Studies of tuberculosis have analyzed the
cancer cells while boosting anti-tumor immune responses, connections between specific genes and various aspects of
offering a new strategy for future cancer therapies. In the disease. Some researchers have identified a potentially
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bacteria, copper activates the response regulator CopR, important role for these genes in the association between
which regulates the rearrangement of lipid proteins and the cuproptosis and tuberculosis. However, due to insufficient
expression of copper resistance genes, thereby reducing the biological evidence and experimental validation, these
immunostimulatory properties of lipid proteins from high studies have only indirectly demonstrated a link between
to low. This mechanism may be commonly present in other cuproptosis and tuberculosis. Whether cuproptosis directly
Firmicutes as well. The following strategies are proposed contributes to the pathogenesis of tuberculosis or impacts
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to combat bacterial copper-related resistance mechanisms: its progression remains unclear.
(i) developing inhibitors that specifically target copper
resistance genes to disrupt the copper tolerance mechanisms The discovery of cuproptosis enhances our
of bacteria. This approach aims to prevent bacteria from understanding of tuberculosis and its underlying molecular
effectively handling high copper environments, thereby mechanisms. Cuproptosis may also hold potential value
weakening their survival and growth capabilities; (ii) in drug screening for treating this disease. Future research
designing inhibitors against the copper sensor CopR. could focus on developing strategies to lower intracellular
By blocking CopR, the bacteria’s ability to sense changes copper levels or inhibit copper transport proteins, leveraging
in copper levels is impaired, which, in turn, disrupts the chelating effects of copper chelators. This opens up new
the downstream regulatory pathways related to copper avenues for intervention in the treatment of tuberculosis. In
response; (iii) developing inhibitors directed at the copper addition, copper can be transported into cells using copper
transport protein CopT. These inhibitors are intended to ion carriers to increase intracellular copper levels. However,

Volume 2 Issue 1 (2025) 65 doi: 10.36922/mi.5657