Mycobacterial P1-Type ATPases Mediate Resistance to Zinc Poisoning in Human Macrophages
Year: 2011
Type: article
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.
Source: Cell Host & Microbe
Authors: Hélène Botella, Pascale Peyron, Florence Levillain, Renaud Poincloux, Yannick Poquet, Irène Brandli, Chuan Wang, Ludovic Tailleux, Sylvain Tilleul, Guillaume M. Charrière, Simon J. Waddell, Maria Foti, Geanncarlo Lugo-Villarino, Qian Gao, Isabelle Maridonneau-Parini, Philip D. Butcher, Paola Ricciardi Castagnoli, Brigitte Gicquel, Chantal de Chastellier, Olivier Neyrolles
Institutions: Centre National de la Recherche Scientifique, Université Toulouse III - Paul Sabatier, Institut de Pharmacologie et de Biologie Structurale, Université de Toulouse, Inserm, Aix-Marseille Université, Centre d’Immunologie de Marseille-Luminy, Shanghai Medical College of Fudan University, Fudan University, Institut Pasteur, Brighton and Sussex Medical School, University of Sussex, University of Milano-Bicocca, St George's, University of London, Singapore Immunology Network
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $10,400
Funder: Wellcome Trust
OpenAlex ID: W2128702173