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
Flagged first, then by citations
Cited by
Sorted by citations
Items 301–380 of 380
The Metallothionein-Zinc Landscape: How It Shapes Antimicrobial Immunity
Chowdhury, D., Deepe, G. S., & Vignesh, K. S. (2019) · Springer eBooks · doi:10.1007/978-981-15-0557-7_4 · Cited by 3
Huang, C.-C., Becerra, M. C., Calderon, R., Contreras, C., Galea, J. T., Grandjean, L., Lecca, L. W., Yataco, R. M., Zhang, Z., & Murray, M. B. (2018) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/479865 · Cited by 3
Dupuy, P., Boudehen, Y., Faucher, M., Buglino, J. A., Fay, A., Cantaloube, S., Grimoire, Y., Marcoux, J., Levet, F., Bettarel, L., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.03.25.645379 · Cited by 3
Self-citationShrestha, S., Shrestha, B. K., Auniq, R. B. Z., Parajuli, N., Desai, S. S., & Bhattarai, N. (2026) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.5c16589 · Cited by 2
Enhanced strategies for cuproptosis‐like death in bacterial infection treatment
Wang, W., Xu, B., Zhu, R., Gui, H., Xia, T., Shaokai, L. I. U., Liu, H., & Wang, X. (2026) · BMEMat · doi:10.1002/bmm2.70089 · Cited by 2
The role of macrophages in tuberculosis
Sikder, M. H., Hossen, M. J., Matin, M. A., Rahman, M., Ahmed, M. S., Asadazzuaman, M., & Islam, A. (2022) · Elsevier eBooks · doi:10.1016/b978-0-12-822368-0.00017-7 · Cited by 2
Li, X., Chen, L., Wang, Y., Guo, X., & He, Z. (2023) · Microbiology Spectrum · doi:10.1128/spectrum.01069-23 · Cited by 2
Waddell, S. J., von Kamp, A., Klamt, S., & Neyrolles, O. (2012) · Springer eBooks · doi:10.1007/978-1-4614-4966-9_6 · Cited by 2
Self-citationRola, A., Wieczorek, R., Kozłowski, H., Krzywoszyńska, K., & Potocki, S. (2021) · Dalton Transactions · doi:10.1039/d1dt01690c · Cited by 2
Evolution of Cell-Autonomous Effector Mechanisms in Macrophages versus Non-Immune Cells
Gaudet, R. G., Bradfield, C. J., & MacMicking, J. D. (2017) · ASM Press eBooks · doi:10.1128/9781555819194.ch34 · Cited by 2
Rockwood, N., Lai, R., Seldon, R., Young, D. B., & Wilkinson, R. J. (2019) · Wellcome Open Research · doi:10.12688/wellcomeopenres.15332.1 · Cited by 2
Moideen, K., Gunasekaran, H., Loukrakpam, B., Ahamed, S. F., Kumar, N. P., Rajendran, A., Bethunaickan, R., & Babu, S. (2025) · Frontiers in Nutrition · doi:10.3389/fnut.2025.1666416 · Cited by 1
Deciphering macrophage dynamics and immune evasion strategies by the intracellular bacteria
Munir, F., He, B., Shakoor, A., Liu, J., & Ma, W. (2025) · Immunologic Research · doi:10.1007/s12026-025-09696-5 · Cited by 1
Schuindt, C. P., Batista, B. B., Cesetti, L., Neto, S. P. L., Soldati, T., & Neto, J. F. D. S. (2026) · BioMetals · doi:10.1007/s10534-026-00828-4 · Cited by 1
Tarique, A. A., Emming, S., Kelk, D., Logan, J., Ramnath, D., Dalton, E. K., Gupta, K. D., Blake, T. L., Curson, J. E. B., Afroz, S. F., et al. (2026) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2537320123 · Cited by 2
Antimycobacterial Agents: To Target or Not to Target
Sajid, A., Arora, G., Virmani, R., & Singhal, A. (2017) · Springer eBooks · doi:10.1007/978-3-319-52669-0_4 · Cited by 1
Basics of tuberculosis disease and principles of treatment and their effects
Shakila, H., Vijayakumar, K. K., Sounderrajan, V., Ramasamy, P., & Rajadas, S. E. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-819985-5.00011-5 · Cited by 2
Hit Compounds and Associated Targets in Intracellular Mycobacterium tuberculosis
Tsui, C. K. M., Sorrentino, F., Narula, G. S., Mendoza-Losana, A., del Río, R. G., Pérez‐Herrán, E., Moure, A. L., Bojang, A. L., Zheng, X., Remuiñán, M. J., et al. (2022) · Molecules · doi:10.3390/molecules27144446 · Cited by 2
Multiomics technologies applied to tuberculosis drug discovery
Ayaz, O., Ali, A., Ayaz, A., Nazir, A., Ahmad, S. B., Alauddin, Singh, N., Wani, A. B., & Bhat, K. A. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-23971-7.00011-0 · Cited by 1
Liu, M. J., & Knoell, D. L. (2014) · Springer eBooks · doi:10.1007/978-4-431-55114-0_11 · Cited by 1
Un rôle nouveau des métaux de transition dans l’immunité antimicrobienne
Botella, H., Stadthagen, G., de Chastellier, C., & Neyrolles, O. (2012) · médecine/sciences · doi:10.1051/medsci/2012281006 · Cited by 1
Self-citationATPasas tipo P2 como blancos para la atenuación de Mycobacterium tuberculosis.
Maya-Hoyos, M. (2021) · Cited by 1
Interaction of Inflammatory Molecules in Tuberculosis and Sars Cov-2 Infection
Purkait, P. (2022) · Virology & Immunology Journal · doi:10.23880/vij-16000286 · Cited by 1
P-Type ATPases: A Relevant Component in Mycobacterium tuberculosis Viability
Santos, P., Maya-Hoyos, M., López-R, M., Rosales, C., Vásquez, V., Varón, A., Chavarro, B., Arenas, N. E., & Soto, C. Y. (2023) · Integrated science · doi:10.1007/978-3-031-15955-8_22 · Cited by 1
Mechanisms of antibiotic resistance and pathogenesis in Acinetobacter baumannii
Hood, M. I. (2012) · Cited by 1
Interplay of human macrophages and Mycobacterium tuberculosis phenotypes
Raffetseder, J. (2016) · doi:10.3384/diss.diva-132321 · Cited by 1
Variation in Host-Pathogen Interactions among Genetically Diverse Strains of Group B Streptococcus
Korir, M. L. (2016) · Michigan State University Libraries · doi:10.25335/7whh-5f88 · Cited by 1
Mehdiratta, K., Singh, S., Sharma, S., Bhosale, R. S., Choudhury, R., Masal, D. P., Manocha, A., Dhamale, B. D., Khan, N. A., Vivekanand, A., et al. (2021) · doi:10.21203/rs.3.rs-226693/v1 · Cited by 1
Serafini, A., Pisu, D., PalÃ, G., Rodríguez, G. M., & Manganelli, R. (2014) · PLoS ONE · doi:10.1371/annotation/56401af3-74aa-4c4f-882c-06481b29aa94 · Cited by 1
Choi, Y., Vo, P. T., Park, J., Kim, H.-J., Yoon, H., & Chang, S.-H. (2024) · Research Square · doi:10.21203/rs.3.rs-3913717/v1 · Cited by 1
Midya, V., Agrawal, M., Lane, J. M., Gennings, C., Tarassishin, L., Torres-Olascoaga, L. A., Eggers, J., Picker, M., Peter, I., Faith, J. J., et al. (2024) · SSRN Electronic Journal · doi:10.2139/ssrn.4764788 · Cited by 1
Bernard, L. (2020) · theses.fr (ABES) · doi:10.70675/589a776dz18d9z4813z9d6fzd73632aa4df7 · Cited by 1
Neutrophils versus Pathogenic Fungi : through the magnifying glass of nutritional immunity
Niemiec, M. J. (2015) · DiVA at Umeå University (Umeå University)
Sanyi, R. H. H. (2016) · Figshare
Metal ion Toxicity and Oxidative Stress inStreptococcus Pneumoniae
McDevitt, C. A., Begg, S. L., & Paton, J. C. (2016) · Wiley eBooks · doi:10.1002/9781119004813.ch115
Zinc: An Immunomodulator of Innate Defense against Pathogenic Infection
Vignesh, K. S. (2013) · OhioLink ETD Center (Ohio Library and Information Network)
Microreview The innate immune response in human tuberculosis
Lerner, T. R., Borel, S., & Gutierrez, M. G. (2015)
WITHDRAWN: Non-infectious stressors and innate immune response
Werling, D. (2018) · Research in Veterinary Science · doi:10.1016/j.rvsc.2018.01.003
RetractedCellular role of the inhibitor-chaperone CpxP in Escherichia coli
Wong, J. L. (2015) · ERA: Education and Research Archive (University of Alberta) · doi:10.7939/r30k26q1v
The Co-Transcriptional Response of Intracellular Group B Streptococcus (GBS) and Monocytes
Prince, D. (2019) · Griffith Research Online · doi:10.25904/1912/1117
Antimicrobial zinc toxicity in Mϕs: ZnT1 pays the toll
Neyrolles, O. (2020) · Journal of Leukocyte Biology · doi:10.1002/jlb.4ce0520-256r · Cited by 2
Self-citationRuíz, S., & Andrea, P. (2020)
Intracellular Drug Targets In Mycobacterium Tuberculosis Revealed By A Chemo-Genetic ApproachPreprint
Tsui, C. K. M., Sorrentino, F., Gagandeep, N., Mendoza-Losana, A., del Río, R. G., Pérez‐Herrán, E., Lopez, A., Bojang, A. L., Zheng, X., Remuiñán, M. J., et al. (2021) · Research Square · doi:10.21203/rs.3.rs-946186/v1
Kana, B. D. (2021) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.740134272.793585908
Skaar, E. P., & Palmer, L. D. (2019) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.736478388.793565991
The Sculpting of theMycobacterium tuberculosisGenome by Host Cell-Derived Pressures
Russell, D. G., Lee, W., Tan, S., Sukumar, N., Podinovskaia, M., Fahey, R. J., & VanderVen, B. C. (2015) · ASM Press eBooks · doi:10.1128/9781555818845.ch35
Maure, A., Lawarée, E., Fiorentino, F., Pawlik, A., Gona, S., Giraud-Gatineau, A., Eldridge, M. J. G., Danckaert, A., Hardy, D., Frigui, W., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.07.21.549986
Self-citationPrice, S. L. (2023) · ThinkIR: The University of Louisville's Institutional Repository (University of Louisville) · doi:10.18297/etd/4087
Overexpression of Ribosomal Proteins Leads to Zn Resistance in Escherichia coliPreprint
Kosaki, T., Shirakawa, R., Ishikawa, K., Furuta, K., & Kaito, C. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.10.02.616313
Chalkophore mediated respiratory oxidase flexibility controls M. tuberculosis virulencePreprint
Buglino, J. A., Ozakman, Y., Hatch, C. E., Benjamin, A., Tan, D. S., & Glickman, M. S. (2025) · eLife · doi:10.7554/elife.105794.1
Chalkophore mediated respiratory oxidase flexibility controls M. tuberculosis virulencePreprint
Buglino, J. A., Ozakman, Y., Hatch, C. E., Benjamin, A., Tan, D. S., & Glickman, M. S. (2025) · eLife · doi:10.7554/elife.105794.2
From Phagosomes to Niches: Macrophage Biology in Tuberculosis RevisitedPreprint
Dupuy, P., Monard, S., Neyrolles, O., & Lugo‐Villarino, G. (2025) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a041819 · Cited by 1
Self-citationImmunometabolic Responses upon Bacterial Infections
Soni, V., & Upadhyay, A. (2026) · Springer eBooks · doi:10.1007/978-3-031-46895-7_8
von Pein, J. B., Andersen, S. B., Xu, J., Phan, M., Dalton, E. K., Koczerka, M., Stocks, C. J., Curson, J. E. B., Vandeleur, Z., Condon, N. D., et al. (2026) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2530503123
Characterisation of Two Novel COG0523-Family Members of the Agrobacterium tumefaciens Zur Regulon
Dubbs, J. M., Nawarathne, N. W., & Mongkolsuk, S. (2026) · European Journal of Biology · doi:10.26650/eurjbiol.2026.1821570
Impact des antibiotiques sur la réponse des macrophages humains : l'exemple de la bédaquiline
Giraud-Gatineau, A. (2019) · theses.fr (ABES) · doi:10.70675/e7540acaz0a22z4dcfz8d5azdf6f3232c4b4
Rôle du microbiote dans les interactions hôte-pathogène dans la tuberculose
Dumas, A. (2018) · theses.fr (ABES) · doi:10.70675/6773a408zdb52z44bbzb51ez3998deaf3ded
Mécanismes de l’homéostasie du cuivre chez un pathogène strictement humain, Bordetella pertussis
Rivera-Millot, A. (2020) · theses.fr (ABES) · doi:10.70675/2af44bf7ze41ez41ecz9697z81ed156fc7d6
Arnett, E., Lumbreras, M., Hernandez, E., Campos, D., Wager, C. M. L., Pahari, S., Matouba, D., Determann, B. F., Renshaw, C., Longstreet, B., et al. (2026) · iScience · doi:10.1016/j.isci.2026.116276
Zhu, J., Wu, B., Luo, M., Peng, Y., Yang, F., Liu, L., Wang, Z., & Huang, D. (2026) · Chemical Engineering Journal · doi:10.1016/j.cej.2026.178732
Zinc: An Emerging Axis of Host–Pathogen Interaction in Tuberculosis
Holl, J., Corro, J. H., Mishra, B. B., & Ojha, A. K. (2026) · Vaccines · doi:10.3390/vaccines14070567
Effluxosomes: A new layer of spatial control in bacterial metal homeostasis
Neyrolles, O. (2026) · doi:10.52843/cassyni.vctxzp.2
Self-citationMichaud‐Soret, I., Neyrolles, O., & Louro, R. O. (2026) · doi:10.52843/cassyni.vctxzp
Self-citation张晓娟, Liu, Y., Hou, Y., & Niu, H. (2026) · MedComm · doi:10.1002/mco2.70884
Butler, R. E., Barber, J., Mayson, G., Wallis, G., & Stewart, G. R. (2026) · Frontiers in Microbiology · doi:10.3389/fmicb.2026.1882584
Virulence regulation in the fish pathogen Pseudomonas plecoglossicida: an integrated overview
Mao, M., & Yan, Q. (2026) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2026.1928252
ZnO nanowires exacerbate bacterial lung infection by dramatically releasing Zn2+ in macrophages
Li, Y., Wang, Q., Xia, H., Wang, F., Song, M., & Jiang, G. (2026) · Journal of Environmental Sciences · doi:10.1016/j.jes.2026.105762
King, S., Malan, L., Visagie, J., Hayford, F. E. A., Zandberg, L., Dolman, R., & Nienaber, A. (2026) · Nutrition Reviews · doi:10.1093/nutrit/nuag134
Rajasekaran, D. S., Rengaraj, S., Kaliamurthi, S., & Selvaraj, G. (2026) · Research Square · doi:10.21203/rs.3.rs-11371300/v1
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