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A copper uptake ABC transport system is essential for Mycobacterium tuberculosis virulence

Zhihong Xu1, Huang Tang2, Meiyi Yan3

  • 1Department of Critical Care Medicine and Emergency, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.

Emerging Microbes & Infections
|May 5, 2026
PubMed

Insights

Mycobacterium tuberculosis uses a copper uptake ABC transporter (Rv1273c-Rv1272c) to import copper, which is essential for its survival and virulence within macrophages.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Pathogenesis

Background:

  • Mycobacterium tuberculosis (Mtb) resides within macrophages, manipulating host cell processes for survival.
  • Copper has a dual role in host-pathogen interactions, acting as both a toxin and a nutrient.
  • The copper uptake mechanisms in Mtb are not well understood, unlike its resistance pathways.

Purpose of the Study:

  • To characterize the copper uptake machinery in Mtb.
  • To investigate the role of Rv1273c and Rv1272c in copper import and Mtb pathogenesis.

Main Methods:

  • Identification and characterization of Rv1273c and Rv1272c as a heterodimeric copper influx ABC transporter.
  • Analysis of gene expression induction by copper and phagocytosis.
  • Assessment of copper's effects on Mtb cell structure, transcriptome, metabolome, and envelope composition.
  • Evaluation of the Rv1273c-Rv1272c deletion mutant in a murine model of infection.

Main Results:

  • Rv1273c and Rv1272c form a copper influx ABC transporter induced by copper and phagocytosis.
  • Imported copper alters Mtb sedimentation, envelope structure, transcriptome, metabolome, and lipid content.
  • Deletion of Rv1273c-Rv1272c significantly reduces bacterial burden in mouse lungs and spleens.

Conclusions:

  • The Rv1273c-Rv1272c ABC transporter is crucial for Mtb copper uptake.
  • Copper import facilitates Mtb survival and pathogenesis within macrophages.
  • This copper uptake system represents a potential target for anti-TB therapies.
Keywords:
ABC transporterCopper uptakeMycobacterium tuberculosisMycolicibacterium smegmatisrv1273c-rv1272c

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