Mycobacterial p(1)-type ATPases mediate resistance to zinc poisoning in human macrophages

Botella, Hélène, Peyron, Pascale, Levillain, Florence, Poincloux, Renaud, Poquet, Yannick, Brandli, Irène, Wang, Chuan, Tailleux, Ludovic, Tilleul, Sylvain, Charrière, Guillaume M, Waddell, Simon J, Foti, Maria, Lugo-Villarino, Geanncarlo, Gao, Qian, Maridonneau-Parini, Isabelle, Butcher, Philip D, Castagnoli, Paola Ricciardi, Gicquel, Brigitte, de Chastellier, Chantal and Neyrolles, Olivier (2011) Mycobacterial p(1)-type ATPases mediate resistance to zinc poisoning in human macrophages. Cell Host and Microbe, 10 (3). pp. 248-259. ISSN 1931-3128

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Abstract

Mycobacterium tuberculosis thrives within macrophages by residing in phagosomes and preventing them from maturing and fusing with lysosomes. A parallel transcriptional survey of intracellular mycobacteria and their host macrophages revealed signatures of heavy metal poisoning. In particular, mycobacterial genes encoding heavy metal efflux P-type ATPases CtpC, CtpG, and CtpV, and host cell metallothioneins and zinc exporter ZnT1, were induced during infection. Consistent with this pattern of gene modulation, we observed a burst of free zinc inside macrophages, and intraphagosomal zinc accumulation within a few hours postinfection. Zinc exposure led to rapid CtpC induction, and ctpC deficiency caused zinc retention within the mycobacterial cytoplasm, leading to impaired intracellular growth of the bacilli. Thus, the use of P(1)-type ATPases represents a M. tuberculosis strategy to neutralize the toxic effects of zinc in macrophages. We propose that heavy metal toxicity and its counteraction might represent yet another chapter in the host-microbe arms race.

Item Type: Article
Subjects: Q Science > Q Science (General)
Q Science > QR Microbiology > QR0075 Bacteria
Q Science > QR Microbiology > QR0180 Immunology
Depositing User: Simon Waddell
Date Deposited: 17 Jul 2012 13:21
Last Modified: 07 Mar 2017 06:43
URI: http://sro.sussex.ac.uk/id/eprint/7645

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