Cu2+ mediates the oxidation of the transcription factor MscA to regulate the antioxidant defense of mycobacteria.

Publication date: Jan 07, 2025

Copper (Cu), a trace element with redox activity, is both essential and toxic to living organisms. Its redox properties make it a cofactor for a variety of proteins, but it also causes oxidative stress, hence the need to maintain intracellular copper homeostasis. However, the role of copper in the regulation of antioxidant defense in bacteria remains unclear, and the involved transcription factors remain to be explored. In this study, we identified a novel transcription factor, MscA, that responded directly to Cu2+ to regulate the antioxidant defense of mycobacteria. Cu2+ directly bound to MscA to mediate oxidation and inhibit the DNA binding activity of MscA, subsequently downregulating the expression of antioxidant gene cluster to increase the accumulation of reactive oxygen species in mycobacteria, ultimately leading to oxidative damage to mycobacteria. Therefore, we firstly reported that the Cu2+ responsive transcription factor regulated the antioxidant defense in bacteria. This finding firstly and directly links the function of Cu2+ to the antioxidant defense of bacteria, and provides a new insight into bacterial antioxidant defense.

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Concepts Keywords
Copper Antioxidants
Homeostasis Antioxidants
Mycobacteria Bacterial Proteins
Nucleic Bacterial Proteins
Toxic Copper
Copper
Mycobacterium
Oxidation-Reduction
Oxidative Stress
Reactive Oxygen Species
Reactive Oxygen Species
Transcription Factors
Transcription Factors

Semantics

Type Source Name
drug DRUGBANK Copper
drug DRUGBANK ANX-510
disease MESH causes
disease MESH oxidative stress
disease IDO role
disease IDO bacteria
drug DRUGBANK Oxygen
drug DRUGBANK Guanosine
drug DRUGBANK Coenzyme M
drug DRUGBANK Creatinolfosfate
drug DRUGBANK Isoxaflutole
drug DRUGBANK Pinaverium
pathway REACTOME Reproduction
pathway REACTOME Translation
disease IDO site
drug DRUGBANK Hydrogen peroxide
drug DRUGBANK L-Cysteine
disease MESH physical barrier
drug DRUGBANK Isopropyl beta-D-thiogalactopyranoside
drug DRUGBANK Imidazole
disease IDO assay
drug DRUGBANK Glycerin
drug DRUGBANK Potassium Chloride
drug DRUGBANK Cysteamine
drug DRUGBANK Edetic Acid
drug DRUGBANK Urea
drug DRUGBANK Dimethyl sulfone
disease IDO colony
drug DRUGBANK Dacarbazine
disease MESH infection
disease IDO host
disease MESH dissociation
disease MESH repression
drug DRUGBANK Cupric cation
drug DRUGBANK Methylergometrine
disease IDO protein
disease IDO process
disease IDO virulence
pathway REACTOME Innate Immune System
drug DRUGBANK (S)-Des-Me-Ampa
drug DRUGBANK Iron
pathway REACTOME Metabolism
pathway KEGG Ferroptosis
pathway REACTOME Mycothiol biosynthesis
disease MESH drug tolerance
disease MESH tuberculosis
pathway KEGG Tuberculosis
disease IDO cell
drug DRUGBANK BCG vaccine
disease MESH death
disease MESH bacterial infection

Original Article

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