The DOI matches its Crossref record; 48 of the 48 references it cites were found in a registry or an index.
Mycobacterial P1-Type ATPases Mediate Resistance to Zinc Poisoning in Human Macrophages
Open accessAbstract
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cited source says what the claim attributes to it.
In the citing paper
“Loss of Zn detoxification machinery in several bacterial pathogens, including Group A and B streptococci 166 , M. tuberculosis and S. pneumoniae , results in decreased intracellular survival 167-170 or in vivo survival in mouse models of infection 169 .”
From Nutritional immunity: the battle for nutrient metals at the host–pathogen interface (2022) · cites this paper as [167]
In the citing paper
“As with copper, M. tuberculosis express p-type ATPase to promote zinc efflux and to resist metal intoxication (239, 242).”
From Macrophage defense mechanisms against intracellular bacteria (2015) · cites this paper as [242]
In the citing paper
“Transcriptional profiling of M. tuberculosis in human macrophages identified signs of metal intoxication in bacteria and in the host, revealing a burst of free zinc in macrophages and intraphagosomal zinc accumulation (18).”
From Transition Metals and Virulence in Bacteria (2016) · cites this paper as [18]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence
Cole, S. T., Brosch, R., Parkhill, J., Garnier, T., Churcher, C., Harris, D., Gordon, S. V., Eiglmeier, K., Gas, S., Barry, C. E., et al. (1998) · Nature · doi:10.1038/31159 · Cited by 7,847
Exaptation—a missing term in the science of form
Gould, S. J., & Vrba, E. S. (1982) · Paleobiology · doi:10.1017/s0094837300004310 · Cited by 5,136
The Essential Toxin: Impact of Zinc on Human Health
Plum, L. M., Rink, L., & Haase, H. (2010) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph7041342 · Cited by 1,577
Natural resistance to infection with intracellular parasites: isolation of a candidate for Bcg
Vidal, S. M., Malo, D., Vogan, K., Skamene, E., & Gros, P. (1993) · Cell · doi:10.1016/0092-8674(93)90135-d · Cited by 1,104
Synthetic fluorescent sensors for studying the cell biology of metals
Domaille, D. W., Que, E. L., & Chang, C. J. (2008) · Nature Chemical Biology · doi:10.1038/nchembio.69 · Cited by 1,085
Armstrong, J. A., & Hart, P. D. (1971) · The Journal of Experimental Medicine · doi:10.1084/jem.134.3.713 · Cited by 991
Regulation of metallothionein gene expression by oxidative stress and metal ions
Andrews, G. K. (2000) · Biochemical Pharmacology · doi:10.1016/s0006-2952(99)00301-9 · Cited by 834
Mammalian Zinc Transporters: Nutritional and Physiologic Regulation
Lichten, L. A., & Cousins, R. J. (2009) · Annual Review of Nutrition · doi:10.1146/annurev-nutr-033009-083312 · Cited by 749
Nutritional immunity beyond iron: a role for manganese and zinc
Kehl-Fie, T. E., & Skaar, E. P. (2010) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2009.11.008 · Cited by 634
Zinc is a novel intracellular second messenger
Yamasaki, S., Sakata-Sogawa, K., Hasegawa, A., Suzuki, T., Kabu, K., Sato, E., Kurosaki, T., Yamashita, S., Tokunaga, M., Nishida, K., et al. (2007) · Journal of Cell Biology · doi:10.1083/jcb.200702081 · Cited by 592
De Voss, J. J., Rutter, K., Schroeder, B. G., Su, H., Zhu, Y., & Barry, C. E. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.3.1252 · Cited by 532
A Role for the ATP7A Copper-transporting ATPase in Macrophage Bactericidal Activity
White, C., Lee, J., Kambe, T., Fritsche, K., & Petris, M. J. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.070201 · Cited by 524
Graham, J. E., & Clark‐Curtiss, J. E. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.20.11554 · Cited by 450
Wagner, D., Maser, J. M., Lai, B. C. H., Cai, Z., Barry, C. E., zu Bentrup, K. H., Russell, D. G., & Bermudez, L. E. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.174.3.1491 · Cited by 430
Efficient allelic exchange and transposon mutagenesis in Mycobacterium tuberculosis
Pelicic, V., Jackson, M., Reyrat, J., Jacobs, W. R., Gicquel, B., & Guilhot, C. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.20.10955 · Cited by 423
Self-citationThe Function of Zinc Metallothionein: A Link between Cellular Zinc and Redox State
Maret, W. (2000) · Journal of Nutrition · doi:10.1093/jn/130.5.1455s · Cited by 417
Gee, K. R., Zhou, Z., Qian, W., & Kennedy, R. T. (2002) · Journal of the American Chemical Society · doi:10.1021/ja011774y · Cited by 406
The structure and function of heavy metal transport P1B-ATPases
ARGÜELLO, J. M., Eren, E., & González‐Guerrero, M. (2007) · BioMetals · doi:10.1007/s10534-006-9055-6 · Cited by 391
Mycobacterium tuberculosis and the environment within the phagosome
Rohde, K. H., Yates, R. M., Purdy, G. E., & Russell, D. G. (2007) · Immunological Reviews · doi:10.1111/j.1600-065x.2007.00547.x · Cited by 372
A membrane protein preserves intrabacterial pH in intraphagosomal Mycobacterium tuberculosis
Vandal, O. H., Pierini, L. M., Schnappinger, D., Nathan, C. F., & Ehrt, S. (2008) · Nature Medicine · doi:10.1038/nm.1795 · Cited by 368
Toll-like receptor–mediated regulation of zinc homeostasis influences dendritic cell function
Kitamura, H., Morikawa, H., Kamon, H., Iguchi, M., Hojyo, S., Fukada, T., Yamashita, S., Kaisho, T., Akira, S., Murakami, M., et al. (2006) · Nature Immunology · doi:10.1038/ni1373 · Cited by 355
Mycobacterial Esx-3 is required for mycobactin-mediated iron acquisition
Siegrist, M. S., Unnikrishnan, M., McConnell, M. J., Borowsky, M. L., Cheng, T., Siddiqi, N., Fortune, S. M., Moody, D. B., & Rubin, E. J. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0900589106 · Cited by 347
CsoR is a novel Mycobacterium tuberculosis copper-sensing transcriptional regulator
Liu, T., Ramesh, A., Ma, Z., Ward, S. K., Zhang, L., George, G. N., Talaat, A. M., Sacchettini, J. C., & Giedroc, D. P. (2007) · Nature Chemical Biology · doi:10.1038/nchembio844 · Cited by 338
Intracellular zinc homeostasis and zinc signaling
Murakami, M., & Hirano, T. (2008) · Cancer Science · doi:10.1111/j.1349-7006.2008.00854.x · Cited by 333
Copper resistance is essential for virulence of Mycobacterium tuberculosis
Wolschendorf, F., Ackart, D., Shrestha, T. B., Hascall-Dove, L., Nolan, S., Lamichhane, G., Wang, Y., Bossmann, S. H., Basaraba, R. J., & Niederweis, M. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1009261108 · Cited by 332
Cellular zinc sensors: MTF-1 regulation of gene expression
Andrews, G. K. (2001) · BioMetals · doi:10.1023/a:1012932712483 · Cited by 325
Rodríguez, G. M., & Smith, I. (2005) · Journal of Bacteriology · doi:10.1128/jb.188.2.424-430.2006 · Cited by 257
Oxidative Stress Activates Metal-responsive Transcription Factor-1 Binding Activity
Dalton, T. P., Li, Q., Bittel, D., Liang, L., & Andrews, G. K. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.42.26233 · Cited by 237
Zinc transporter ZIP8 (SLC39A8) and zinc influence IFN-γ expression in activated human T cells
Aydemir, T. B., Liuzzi, J. P., McClellan, S., & Cousins, R. J. (2009) · Journal of Leukocyte Biology · doi:10.1189/jlb.1208759 · Cited by 229
Glutathione and Transition-Metal Homeostasis in Escherichia coli
Helbig, K., Bleuel, C., Krauss, G.-J., & Nies, D. H. (2008) · Journal of Bacteriology · doi:10.1128/jb.00271-08 · Cited by 218
Karyadi, E., West, C. E., Schultink, W., Nelwan, R. H. H., Gross, R., Amin, Z., Dolmans, W. M. V., Schlebusch, H., & van der Meer, J. W. M. (2002) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/75.4.720 · Cited by 209
Tailleux, L., Waddell, S. J., Pelizzola, M., Mortellaro, A., Withers, M., Tanne, A. J., Castagnoli, P. R., Gicquel, B., Stoker, N. G., Butcher, P. D., et al. (2008) · PLoS ONE · doi:10.1371/journal.pone.0001403 · Cited by 206
Self-citationNramp1 phagocyte intracellular metal withdrawal defense
Cellier, M. F., Courville, P., & Campion, C. (2007) · Microbes and Infection · doi:10.1016/j.micinf.2007.09.006 · Cited by 203
CtpV: a putative copper exporter required for full virulence of Mycobacterium tuberculosis
Ward, S. K., Abomoelak, B., Hoye, E. A., Steinberg, H. N., & Talaat, A. M. (2010) · Molecular Microbiology · doi:10.1111/j.1365-2958.2010.07273.x · Cited by 198
Protection against zinc toxicity by metallothionein and zinc transporter 1
Palmiter, R. D. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0401022101 · Cited by 197
Iron-cofactored Superoxide Dismutase Inhibits Host Responses to Mycobacterium tuberculosis
Edwards, K. M., Cynamon, M. H., Voladri, R. K. R., Hager, C., DeStefano, M. S., Tham, K. T., LAKEY, D. L., Bochan, M. R., & Kernodle, D. S. (2001) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/ajrccm.164.12.2106093 · Cited by 196
Caminero, J. A., PENA, M. J., Campos-Herrero, M. I., RODRÍGUEZ, J. C., GARCÍA, I., Cabrera, P., Lafoz, C., Samper, S., Takiff, H. E., AFONSO, O., et al. (2001) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/ajrccm.164.7.2101031 · Cited by 179
Regulation of T cell receptor signaling by activation-induced zinc influx
Yu, M., Lee, W., Tomar, D., Pryshchep, S., Cześnikiewicz‐Guzik, M., Lamar, D. L., Li, G., Singh, K., Tian, L., Weyand, C. M., et al. (2011) · The Journal of Experimental Medicine · doi:10.1084/jem.20100031 · Cited by 172
Innate immunity to intracellular pathogens: macrophage receptors and responses to microbial entry
Plüddemann, A., Mukhopadhyay, S., & Gordon, S. (2011) · Immunological Reviews · doi:10.1111/j.1600-065x.2010.00989.x · Cited by 170
Macrophage nutriprive antimicrobial mechanisms
Appelberg, R. (2006) · Journal of Leukocyte Biology · doi:10.1189/jlb.0206079 · Cited by 152
Chan, H., Babayan, V., Blyumin, E., Gandhi, C., Hak, K., Harake, D. E., Kumar, K., Lee, P., Li, T. T., Liu, H. Y., et al. (2010) · Microbial Physiology · doi:10.1159/000319588 · Cited by 116
The many niches and strategies used by pathogenic mycobacteria for survival within host macrophages
de Chastellier, C. (2009) · Immunobiology · doi:10.1016/j.imbio.2008.12.005 · Cited by 114
Cadmium Toxicity in Glutathione Mutants ofEscherichia coli
Helbig, K., Große, C., & Nies, D. H. (2008) · Journal of Bacteriology · doi:10.1128/jb.00272-08 · Cited by 113
A Cadmium-Lead-sensing ArsR-SmtB Repressor with Novel Sensory Sites
Cavet, J. S., Graham, A. I., Meng, W., & Robinson, N. J. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m307877200 · Cited by 79
Beard, S. J., Hughes, M., & Poole, R. K. (1995) · FEMS Microbiology Letters · doi:10.1111/j.1574-6968.1995.tb07778.x · Cited by 76
Immersion autometallographic tracing of zinc ions in Alzheimer beta-amyloid plaques
Stoltenberg, M., Bruhn, M., Søndergaard, C. S., Doering, P., West, M. J., Larsen, A., Troncoso, J. C., & Danscher, G. (2005) · Histochemistry and Cell Biology · doi:10.1007/s00418-005-0787-0 · Cited by 60
Chaperone-mediated Cu+ Delivery to Cu+ Transport ATPases
González‐Guerrero, M., Hong, D., & ARGÜELLO, J. M. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.016329 · Cited by 59
Green, J. A., Lewin, S. R., Wightman, F., Lee, M., Ravindran, T., & Paton, N. I. (2005) · PubMed · Cited by 38
Flagged first, then by citations
Cited by
Sorted by citations
Nutritional immunity: transition metals at the pathogen–host interface
Hood, M. I., & Skaar, E. P. (2012) · Nature Reviews Microbiology · doi:10.1038/nrmicro2836 · Cited by 1,535
Macrophage defense mechanisms against intracellular bacteria
Weiss, G., & Schaible, U. E. (2015) · Immunological Reviews · doi:10.1111/imr.12266 · Cited by 989
Metal homeostasis and resistance in bacteria
Chandrangsu, P., Rensing, C., & Helmann, J. D. (2017) · Nature Reviews Microbiology · doi:10.1038/nrmicro.2017.15 · Cited by 812
The Role of Zinc in Antiviral Immunity
Read, S. A., Obeid, S., Ahlenstiel, C., & Ahlenstiel, G. (2019) · Advances in Nutrition · doi:10.1093/advances/nmz013 · Cited by 801
Nutritional immunity: the battle for nutrient metals at the host–pathogen interface
Murdoch, C. C., & Skaar, E. P. (2022) · Nature Reviews Microbiology · doi:10.1038/s41579-022-00745-6 · Cited by 701
Metadata
- Authors
- Botella, H., Peyron, P., Levillain, F., Poincloux, R., Poquet, Y., Brandli, I., Wang, C., Tailleux, L., Tilleul, S., Charrière, G. M., Waddell, S. J., Foti, M., Lugo-Villarino, G., Gao, Q., Maridonneau-Parini, I., Butcher, P. D., Castagnoli, P. R., Gicquel, B., de Chastellier, C., & Neyrolles, O.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Institut Pasteur (FR)
- Brighton and Sussex Medical School (GB)
- University of Milano-Bicocca (IT)
- Shanghai Medical College of Fudan University (CN)
- St George's, University of London (GB)
- Singapore Immunology Network (SG)
- Corresponding author
- Neyrolles, Olivier
- ORCID
- Venue
- Cell Host & Microbe
- Publisher
- Elsevier BV
- Published
- 2011-09
- Volume
- 10
- Issue
- 3
- Pages
- 248-259
- ISSN
- 1931-3128 (ISSN-L)
- PMC
- PMC3221041
- OpenAlex
- W2128702173
- Cited by
- 381
- References
- 48
- Citations by year
- 2026: 23 · 2025: 20 · 2024: 32 · 2023: 21 · 2022: 27 · 2021: 41 · 2020: 30 · 2019: 32 · 2018: 23 · 2017: 27 · 2016: 19 · 2015: 23 · 2014: 23 · 2013: 21 · 2012: 17
- FWCI
- 13.38
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Cell Host & Microbe (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Sussex Research Online (University of Sussex) (submittedVersion, cc-by)
- HAL (submittedVersion)
- HAL AMU (submittedVersion)
- BOA (University of Milano-Bicocca) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- Funders
- Wellcome Trust (086547)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Health Sciences › Medicine › Epidemiology › Mycobacterium research and diagnosis
- Keywords
- Mycobacterium tuberculosis, zinc efflux, zinc toxicity, metallothionein, ZnT1, phagosome maturation, intracellular bacterial growth, macrophages
- MeSH terms
- Animals, Cells, Cultured, Female, Humans, Macrophages, Mice, Inbred BALB C, Mycobacterium tuberculosis, Tuberculosis, Zinc, Bacterial Proton-Translocating ATPases, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
