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Comment
. 2011 Sep 15;10(3):181-3.
doi: 10.1016/j.chom.2011.08.008.

The galvanizing of Mycobacterium tuberculosis: an antimicrobial mechanism

Affiliations
Comment

The galvanizing of Mycobacterium tuberculosis: an antimicrobial mechanism

David G Russell. Cell Host Microbe. .

Abstract

Evolving under constant threat from invading microbes, macrophages have acquired multiple means of killing bacteria. In this issue of Cell Host & Microbe, Botella and colleagues (Botella et al., 2011) describe a novel antimicrobial mechanism based on elevated levels of intraphagosomal Zn(2+) and the corresponding induction of bacterial genes to ameliorate this host-derived stress.

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Figures

Figure 1
Figure 1
This diagram illustrates the sequence of events that lead to increased Zn2+ concentration within the Mycobacterium tuberculosis-containing phagosome, and the subsequent up-regulation of both host and bacterial genes in response to free Zn2+. During phagocytosis of Mtb the NADPH Oxidase complex is formed on the phagosomal membrane and generates reactive oxygen intermediates (ROIs). These ROIs signal back on the host cell and induce release of free Zn2+ from intracellular stores, such as the mitochondria. The free Zn2+ is transported into the Mtb vacuole and other endosomal compartments through unknown Zn2+ transporters. Within the phagosome, this increase in free Zn2+, which is potentially toxic to Mtb, is countered through the up-regulation of the bacterial Zn2+ efflux pump CtpP. Within the host cell, the increase in cytoplasmic Zn2+ induces the migration of metal regulatory transcriptional factor 1 (MTH1) to the nucleus where it up-regulates transcription of genes encoding metallothioneins and the Zn2+ efflux pump ZnT1. ZnT1 is assembled in the plasmalemma and pumps free Zn2+ out of the infected cell.

Comment on

  • Mycobacterial p(1)-type ATPases mediate resistance to zinc poisoning in human macrophages.
    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. Botella H, et al. Cell Host Microbe. 2011 Sep 15;10(3):248-59. doi: 10.1016/j.chom.2011.08.006. Cell Host Microbe. 2011. PMID: 21925112 Free PMC article.

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