TB R&D Weekly Update: Zinc Used by Host to Fight TB

Botella H, Peyron P, Levillain F, Poincloux R, Poquet Y, Brandli I, Wang C, Tailleux L, Tilleul S, Charrière GM, Waddell SJ, Foti M, Lugo-Villarino G, Gao Q, Maridonneau-Parini I, Butcher PD, Castagnoli PR, Gicquel B, de Chastellier C, Neyrolles O. Mycobacterial p(1)-type ATPases mediate resistance to zinc poisoning in human macrophages. Cell Host Microbe. 2011 Sep 15;10(3):248-59. (Free Featured Article)

This week, we provide an brief overview of research supported by CNRS, INSERM, Institut Pasteur and other donors providing new evidence of the role of Zinc in the body’s immune response to intracellular infection by M.tb. and the microbe’s strategy to subvert this defense. Key points from the article:

  • Macrophages and other phagocytes various defenses to clear intracellular microbes including creating a toxic intracellular environment. Macrophages may make use of heavy metal poisoning using zinc and other free metals as a mechanism of antimicrobial immunity.
  • Botella, et al., used a combination of fluorescence and electron microscopy-based approaches to look at zinc in the intracellular environment in host cells during infection.
  • The exact mechanism(s) of zinc penetration into the bacteria and bacterial killing is still not clearly understood.
  • The bacteria uses ion pumps to flush out heavy metals and counteract the toxic effects of zinc. The large family of ion pumps explored in this research were the P1-type ATPases encoded by genes CtpC, CtpG, and CtpV. Such genes may be possible targets for treatment of M.tb.
  • Zinc trafficking inside host cells may be highly dependent on the cell type being considered.

Additional coverage in News Medical entitled “Immune system uses zinc to destroy tuberculosis bacillus or E. coli”.

Additional R&D News:

The Power of the PDP (Featuring WGND Co-Chair, Mel Spigelman)

TB vaccine research: New network connects European and African institutions

NIH Director’s Awards Go to Three Johns Hopkins Scientists for Work That Challenges the Status Quo and Speeds Translation of Research

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