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Inhibitors of Mycobacterium tuberculosis DosRST signaling and persistence
Abstract
The Mycobacterium tuberculosis (Mtb) DosRST two-component regulatory system promotes the survival of Mtb during non-replicating persistence (NRP). NRP bacteria help drive the long course of tuberculosis therapy; therefore, chemical inhibition of DosRST may inhibit the ability of Mtb to establish persistence and thus shorten treatment. Using a DosRST-dependent fluorescent Mtb reporter strain, a whole-cell phenotypic high-throughput screen of a ∼540,000 compound small-molecule library was conducted. The screen discovered novel inhibitors of the DosRST regulon, including three compounds that were subject to follow-up studies: artemisinin, HC102A and HC103A. Under hypoxia, all three compounds inhibit Mtb-persistence-associated physiological processes, including triacylglycerol synthesis, survival and antibiotic tolerance. Artemisinin functions by disabling the heme-based DosS and DosT sensor kinases by oxidizing ferrous heme and generating heme-artemisinin adducts. In contrast, HC103A inhibits DosS and DosT autophosphorylation activity without targeting the sensor kinase heme.
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NIH Image to ImageJ: 25 years of image analysis
Schneider, C. A., Rasband, W. S., & Eliceiri, K. W. (2012) · Nature Methods · doi:10.1038/nmeth.2089 · Cited by 64,638
Zhang, J.-H., Chung, T. D. Y., & Oldenburg, K. R. (1999) · SLAS Discovery · doi:10.1177/108705719900400206 · Cited by 6,847
Betts, J. C., Lukey, P. T., Robb, L. C., McAdam, R. A., & Duncan, K. (2002) · Molecular Microbiology · doi:10.1046/j.1365-2958.2002.02779.x · Cited by 1,395
Anti-virulence strategies to combat bacteria-mediated disease
Rasko, D. A., & Sperandio, V. (2010) · Nature Reviews Drug Discovery · doi:10.1038/nrd3013 · Cited by 1,383
Inhibition of Respiration by Nitric Oxide Induces a Mycobacterium tuberculosis Dormancy Program
Voskuil, M. I., Schnappinger, D., Visconti, K. C., Harrell, M. I., Dolganov, G., Sherman, D. R., & Schoolnik, G. K. (2003) · The Journal of Experimental Medicine · doi:10.1084/jem.20030205 · Cited by 975
Nonreplicating Persistence of Mycobacterium Tuberculosis
Wayne, L. G., & Sohaskey, C. D. (2001) · Annual Review of Microbiology · doi:10.1146/annurev.micro.55.1.139 · Cited by 807
Mycobacterium tuberculosis: success through dormancy
Gengenbacher, M., & Kaufmann, S. H. E. (2012) · FEMS Microbiology Reviews · doi:10.1111/j.1574-6976.2012.00331.x · Cited by 722
Park, H., Guinn, K. M., Harrell, M. I., Liao, R., Voskuil, M. I., Tompa, M., Schoolnik, G. K., & Sherman, D. R. (2003) · Molecular Microbiology · doi:10.1046/j.1365-2958.2003.03474.x · Cited by 712
The Transcriptional Responses of Mycobacterium tuberculosis to Inhibitors of Metabolism
Boshoff, H. I., Myers, T. G., Copp, B. R., McNeil, M., Wilson, M. A., & Barry, C. E. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m406796200 · Cited by 603
Self-citationDiscovery of Q203, a potent clinical candidate for the treatment of tuberculosis
Pethe, K., Bifani, P. J., Jang, J., Kang, S., Park, S., Ahn, S., Jiřiček, J., Jung, J., Jeon, H. K., Cechetto, J. D., et al. (2013) · Nature Medicine · doi:10.1038/nm.3262 · Cited by 601
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HspX promotes the polar localization of mycobacterial protein aggregates
Zhang, Y.-W., Zhu, J., Wang, Z., Wu, Y., Meng, X., Zheng, X., & Javid, B. (2019) · Scientific Reports · doi:10.1038/s41598-019-51132-w · Cited by 10
AC2P20 selectively kills Mycobacterium tuberculosis at acidic pH by depleting free thiols
Dechow, S. J., Coulson, G. B., Wilson, M. W., Larsen, S. D., & Abramovitch, R. B. (2021) · RSC Advances · doi:10.1039/d1ra03181c · Cited by 10
Self-citationZhang, J., Ju, Y., Li, L., Hameed, H. M. A., Yusuf, B., Gao, Y., Fang, C., Tian, X., Ding, J., Ma, W., et al. (2025) · International Journal of Antimicrobial Agents · doi:10.1016/j.ijantimicag.2024.107442 · Cited by 9
An oxidatively stressful situation: a case of Artemisia annua L.
Kam, M. Y. Y., & Yap, W. S. P. (2020) · Biotechnology and Genetic Engineering Reviews · doi:10.1080/02648725.2020.1749818 · Cited by 9
Kevorkian, Y. L., MacGilvary, N. J., Giacalone, D., Johnson, C., & Tan, S. (2022) · Molecular Microbiology · doi:10.1111/mmi.14886 · Cited by 8
Unravelling the flexibility of Mycobacterium tuberculosis: an escape way for the bacilli
Sau, S., Roy, A., Agnivesh, P. K., Kumar, S., Guru, S. K., Sharma, S., & Kalia, N. P. (2023) · Journal of Medical Microbiology · doi:10.1099/jmm.0.001695 · Cited by 9
Pushkaran, A. C., Biswas, R., & Mohan, C. G. (2019) · Challenges and advances in computational chemistry and physics · doi:10.1007/978-3-030-05282-9_10 · Cited by 9
Peng, F., Chen, J., Liu, X., Li, Y., Liu, C., Yang, Y., & Bai, Z. (2021) · World Journal of Microbiology and Biotechnology · doi:10.1007/s11274-021-03131-1 · Cited by 8
Apiche, E. A., Yee, E., Damodaran, A. R., & Bhagi‐Damodaran, A. (2024) · Journal of Inorganic Biochemistry · doi:10.1016/j.jinorgbio.2024.112576 · Cited by 8
Chengalroyen, M. D., Jordaan, A., Seldon, R., Ioerger, T. R., Franzblau, S. G., Nasr, M., Warner, D. F., & Mizrahi, V. (2020) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2020.582416 · Cited by 8
Sousa, E. H. S., Diógenes, I. C. N., Lopes, L. G. D. F., & Moura, J. J. G. (2020) · JBIC Journal of Biological Inorganic Chemistry · doi:10.1007/s00775-020-01803-1 · Cited by 8
Vashisth, D., & Mishra, S. (2025) · 3 Biotech · doi:10.1007/s13205-025-04332-3 · Cited by 8
Xie, X., Chen, Q., Guo, C., Zeng, J., & He, Q. (2025) · Frontiers in Pharmacology · doi:10.3389/fphar.2025.1602581 · Cited by 8
Kumari, P., Kumar, S., Kaur, K., Gupta, U. D., Bhagyawant, S. S., & Tyagi, J. S. (2020) · Biochemical Journal · doi:10.1042/bcj20200113 · Cited by 7
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Lv, Z., Zhang, L., Chen, L., Zhang, F., & Tang, K. (2018) · Plant Physiology and Biochemistry · doi:10.1016/j.plaphy.2018.02.033 · Cited by 7
Simcox, B. S., & Rohde, K. H. (2024) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2024.1411333 · Cited by 6
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Chen, Q., Wang, Z., Lv, J., Liu, L., Li, H., Sun, W., Huo, Y., Guo, Y., Shen, C., Li, S., et al. (2022) · Trials · doi:10.1186/s13063-022-06336-3 · Cited by 6
Zhou, Z., Wattiez, R., Constant, P., Marrakchi, H., Soetaert, K., Mathys, V., Fontaine, V., & Zeng, S. (2023) · Microorganisms · doi:10.3390/microorganisms11102469 · Cited by 6
Current state, strategies, and perspectives in enhancing artemisinin production
Zakariya, A. M., Saiman, M. Z., Simonsen, H. T., & Ikram, N. K. K. (2023) · Phytochemistry Reviews · doi:10.1007/s11101-023-09897-6 · Cited by 5
Yang, Y., Xiao, C., Cai, Y., Wang, J., Ruan, Q., Sheng, M., Li, L., Tang, K., Kai, G., & Hao, X. (2023) · Industrial Crops and Products · doi:10.1016/j.indcrop.2023.116769 · Cited by 4
Total synthesis of dissectol A, using an enediolate-based Tsuji–Trost reaction
Andringa, R. L. H., Marinus, N., Bunt, D. V., Haiderer, E. R., Abramovitch, R. B., Brown, C. D., Rhee, K. Y., Witte, M. D., & Minnaard, A. J. (2024) · Chemical Science · doi:10.1039/d4sc01745e · Cited by 4
Self-citationMartini, M. C., Alonso, M. N., Cafiero, J. H., Xiao, J., & Shell, S. S. (2024) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00645-24 · Cited by 4
Redox‐guided small molecule antimycobacterials
Kulkarni, A., Sharma, A., & Chakrapani, H. (2018) · IUBMB Life · doi:10.1002/iub.1867 · Cited by 5
Drug Repurposing for Tuberculosis
Cardoso, N. C., Oosthuizen, C. B., Peton, N., & Singh, V. (2021) · IntechOpen eBooks · doi:10.5772/intechopen.101393 · Cited by 3
Kam, M. Y. Y., & Yap, W. S. P. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/740167 · Cited by 3
Ekness, F., Wold, E. A., Leasure, C. S., Musteata, E., Monteith, A. J., Laut, C. L., Rosato, A. E., Skaar, E. P., & Tabor, J. J. (2025) · ACS Synthetic Biology · doi:10.1021/acssynbio.4c00826 · Cited by 2
Chiarelli, L. R., Lepioshkin, A., Pasca, M. R., & Makarov, V. (2025) · Drug Discovery Today · doi:10.1016/j.drudis.2025.104501 · Cited by 2
Sharma, A., Singh, G., & Shrivastava, R. (2026) · Drug Development Research · doi:10.1002/ddr.70239 · Cited by 3
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Battula, M. S., Bhor, S. S., Bhowmick, S., Eldesoky, G. E., & Chikhale, R. V. (2025) · Chemistry & Biodiversity · doi:10.1002/cbdv.202402926 · Cited by 2
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Zheng, H., & Abramovitch, R. B. (2019) · Springer eBooks · doi:10.1007/978-3-030-25241-0_10 · Cited by 2
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Gao, S., Liu, B., Yuan, S., Quan, Y., Song, S., Jin, W., Wang, Y., & Wang, Y. (2025) · International Journal of Antimicrobial Agents · doi:10.1016/j.ijantimicag.2025.107479 · Cited by 1
Regulation of bacterial phosphorelay systems
Foulkes, D. M., Cooper, D. M., Westland, C., & Byrne, D. P. (2025) · RSC Chemical Biology · doi:10.1039/d5cb00016e · Cited by 1
Vijayalakshmi, P., Alfaiz, F. A., Vijayakumar, R., Desai, D., & Selvaraj, C. (2025) · Microbial Pathogenesis · doi:10.1016/j.micpath.2025.108173 · Cited by 1
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Russell, D. G. (2017) · Nature · doi:10.1038/546044a · Cited by 1
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Johnson, D. I. (2017) · Springer eBooks · doi:10.1007/978-3-319-67651-7_34 · Cited by 1
Hazra, S., & Patra, S. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-820084-1.00030-2 · Cited by 1
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Sergunin, A., Vávra, J., Pašek, D., Shimizu, T., & Martínková, M. (2024) · Advances in microbial physiology/Advances in Microbial Physiology · doi:10.1016/bs.ampbs.2024.10.001 · Cited by 1
ATPasas tipo P2 como blancos para la atenuación de Mycobacterium tuberculosis.
Maya-Hoyos, M. (2021) · Cited by 1
The Mycobacterium tuberculosis: A Silent KillerPreprint
de Oliveira, H. V., Ferreira, J., Matta, A. C., & Oliveira, M. C. (2023) · Preprints.org · doi:10.20944/preprints202309.1841.v1
Genetic and metabolic regulation of Mycobacterium tuberculosis acid growth arrestPreprint
Baker, J. J., & Abramovitch, R. B. (2017) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/186551
Self-citationMolecular Mechanisms and Gene Regulation for Biosynthesis of Medicinal Plant Active Ingredients
Zhang, L., Tan, H., & Zerbe, P. (2019) · Springer eBooks · doi:10.1007/978-981-32-9034-1_8
Sevalkar, R. R., Glasgow, J. N., Pettinati, M., Marti, M. A., Reddy, V. P., Basu, S., Alipour, E., Kim‐Shapiro, D. B., Estrin, D. A., Lancaster, J. R., et al. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.06.21.449194
ABDULKADIR, L. G., ALIERO, A. A., Maishanu, H. M., & Abbas, A. Y. (2022) · Journal of Plant Development · doi:10.47743/jpd.2022.29.1.896
Stupar, M., Tan, L., Kerr, E. D., Voss, C. J. D., Forde, B. M., Schulz, B. L., & West, N. P. (2023) · Research Square · doi:10.21203/rs.3.rs-2847166/v1
Wang, X., Jowsey, W. J., Cheung, C., Seeto, N. E. J., Waller, N. J. E., Chrisp, M. T., Peterson, A. L., Nijagal, B., Fineran, P. C., Cook, G. M., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.12.07.570702
Garg, A. D., Pandit, M., Malhotra, V., & Saini, D. K. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.12.19.571805
Peraman, R., Chilamakuru, N. B., Dusthackeer, A., Varadaraj Bhat, G., Nikhil, P., Aishwarya, D., Nair, D., Pemmadi, R. V., & Reddy, Y. P. (2024) · SSRN Electronic Journal · doi:10.2139/ssrn.4765237
Zhang, J., Ju, Y., Li, L., Hameed, A., Yusuf, B., Gao, Y., Fang, C., Tian, X., Ding, J., Ma, W., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.04.05.588258
ABDULKADIR, L. G., ALIERO, A. A., Maishanu, H. M., & Abbas, A. Y. (2024) · Journal of Plant Development · doi:10.47743/jpd.2024.31.1.964
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Lawrence, A.-L. E., & Tan, S. (2025) · ACS Infectious Diseases · doi:10.1021/acsinfecdis.4c00840
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Wang, W. H., & Gisenya, P. (2025) · Pharmacy & Pharmacology International Journal · doi:10.15406/ppij.2025.13.00460
Eke, I. E., Williams, J. T., & Abramovitch, R. B. (2025) · ACS Infectious Diseases · doi:10.1021/acsinfecdis.4c00936
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Larson, G. W., Yee, E., Damodaran, A. R., & Damodaran, A. R. (2026) · JBIC Journal of Biological Inorganic Chemistry · doi:10.1007/s00775-026-02145-0
Hänscheid, T., del Portal Luyten, C. R., Hermans, S., & Grobusch, M. P. (2024) · Figshare · doi:10.6084/m9.figshare.26715721
Mohammed, S., Dekabo, A., & Hailu, T. (2022) · Figshare · doi:10.6084/m9.figshare.19166845
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Malik, K. A., Razzaq, A., Ghufran, H., Naseer, M. A., Tariq, Y., Abbas, Z., Basit, M. H., Nazir, A., Saeed, A., Bhatti, R., et al. (2019) · International Journal of Biosciences (IJB) · doi:10.12692/ijb/15.2.281-296
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Abdalla, B. J., Giletto, M. B., Carpa, N. G., Wilson, A. K., Ellsworth, E. L., & Abramovitch, R. B. (2026) · ACS Chemical Biology · doi:10.1021/acschembio.5c00709
Self-citationInnovative platforms for drug discovery against mycobacteria: The success and challenges
Nitschke, J., Soldati, T., & Hanna, N. (2026) · Elsevier eBooks · doi:10.1016/b978-0-443-36518-8.00021-7
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Sharma, D., Singh, I., Verma, I. K., Ratn, A., Bisht, D., Dalal, J., & Dhakad, M. S. (2026) · Springer eBooks · doi:10.1007/978-981-92-0256-0_9
Meyer, M. D., Bergkessel, M., & DePas, W. H. (2026) · Journal of Bacteriology · doi:10.1128/jb.00076-26
Reyna, Á. G., Spencer, D. M., Gautam, U., & Pisetsky, D. S. (2026) · ImmunoHorizons · doi:10.1093/immhor/vlag047
BindingDB Entry 50018470: Repurposed drug candidates for antituberculosis therapy.
BindingDB (2024) · UC San Diego · doi:10.7270/q2zk5mvq
Metadata
- Authors
- Zheng, H., Colvin, C. J., Johnson, B. K., Kirchhoff, P. D., Wilson, M., Jorgensen-Muga, K., Larsen, S. D., & Abramovitch, R. B.
- Affiliations
- Michigan State University (US)
- University of Michigan (US)
- Sweet Briar College (US)
- Corresponding author
- Abramovitch, Robert B
- Venue
- Nature Chemical Biology
- Published
- 2016-12-19
- Volume
- 13
- Issue
- 2
- Pages
- 218-225
- ISSN
- 1552-4450 (ISSN-L)
- 1552-4469
- OpenAlex
- W2563595958
- Cited by
- 169
- References
- 56
- Citations by year
- 2026: 7 · 2025: 16 · 2024: 20 · 2023: 19 · 2022: 27 · 2021: 17 · 2020: 15 · 2019: 24 · 2018: 15 · 2017: 9
- FWCI
- 14.76
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Chemical Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases (U54AI057159, R21AI105867)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Life Sciences › Immunology and Microbiology › Applied Microbiology and Biotechnology › Microbial Natural Products and Biosynthesis
- Keywords
- Mycobacterium tuberculosis, non-replicating persistence, dormancy regulation, artemisinin, triglyceride synthesis, antibiotic tolerance, hypoxia, tuberculosis drug discovery, small molecule inhibitors
- MeSH terms
- Histidine Kinase, Dose-Response Relationship, Drug, Mycobacterium tuberculosis, Structure-Activity Relationship, Molecular Structure, Signal Transduction, Artemisinins, Protein Kinase Inhibitors, Drug Discovery
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