The DOI matches its Crossref record; 42 of the 42 references it cites were found in a registry or an index.
Secreted transcription factor controls Mycobacterium tuberculosis virulence
Open accessAbstract
Bacterial pathogens trigger specialized virulence factor secretion systems on encountering host cells. The ESX-1 protein secretion system of Mycobacterium tuberculosis-the causative agent of the human disease tuberculosis-delivers bacterial proteins into host cells during infection and is critical for virulence, but how it is regulated is unknown. Here we show that EspR (also known as Rv3849) is a key regulator of ESX-1 that is required for secretion and virulence in mice. EspR activates transcription of an operon that includes three ESX-1 components, Rv3616c-Rv3614c, whose expression in turn promotes secretion of ESX-1 substrates. EspR directly binds to and activates the Rv3616c-Rv3614c promoter and, unexpectedly, is itself secreted from the bacterial cell by the ESX-1 system that it regulates. Efflux of the DNA-binding regulator results in reduced Rv3616c-Rv3614c transcription, and thus reduced ESX-1 secretion. Our results reveal a direct negative feedback loop that regulates the activity of a secretion system essential for virulence. As the virulence factors secreted by the ESX-1 system are highly antigenic, fine control of secretion may be critical to successful infection.
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“Thus far, four ESX-1 substrates have been identified in addition to ESAT-6 and CFP-10. These substrates are called EspA [39], EspB [46], EspR [41], and the M. marinum homologue of Rv3864 [22].”
From Systematic Genetic Nomenclature for Type VII Secretion Systems (2009) · cites this paper as [41]
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Cites
In silico prediction of protein-protein interactions in human macrophages
Souiai, O., Guerfali, F. Z., Miled, S. B., Brun, C., & Benkahla, A. (2014) · BMC Research Notes · doi:10.1186/1756-0500-7-157 · Cited by 10,785
Significance analysis of microarrays applied to the ionizing radiation response
Tusher, V. G., Tibshirani, R., & Chu, G. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.091062498 · Cited by 10,568
Enhanced genome annotation using structural profiles in the program 3D-PSSM 1 1Edited by J. Thornton
Kelley, L. A., MacCallum, R. M., & Sternberg, M. J. E. (2000) · Journal of Molecular Biology · doi:10.1006/jmbi.2000.3741 · Cited by 1,464
Transcriptional Adaptation of Mycobacterium tuberculosis within Macrophages
Schnappinger, D., Ehrt, S., Voskuil, M. I., Liu, Y., Mangan, J. A., Monahan, I. M., Dolganov, G., Efron, B., Butcher, P. D., Nathan, C., et al. (2003) · The Journal of Experimental Medicine · doi:10.1084/jem.20030846 · Cited by 1,420
Molecular analysis of genetic differences between Mycobacterium bovis BCG and virulent M. bovis
Mahairas, G. G., Sabo, P. J., Hickey, M. J., Singh, D. C., & Stover, C. K. (1996) · Journal of Bacteriology · doi:10.1128/jb.178.5.1274-1282.1996 · Cited by 1,103
Ensoli, B., Buonaguro, L., Barillari, G., Valeria Fiorelli, A., Gendelman, R., Morgan, R. A., Wingfield, P. T., & Gallo, R. C. (1993) · Journal of Virology · doi:10.1128/jvi.67.1.277-287.1993 · Cited by 795
Type VII secretion — mycobacteria show the way
Abdallah, A. M., Gey van Pittius, N. C., DiGiuseppe Champion, P. A., Cox, J., Luirink, J., Vandenbroucke-Grauls, C. M. J. E., Appelmelk, B. J., & Bitter, W. (2007) · Nature Reviews Microbiology · doi:10.1038/nrmicro1773 · Cited by 763
Self-citationHsu, T., Hingley-Wilson, S. M., Chen, B., Chen, M., Dai, A. Z., Morin, P. M., Marks, C. B., Padiyar, J., Goulding, C., Gingery, M., et al. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1635213100 · Cited by 731
Stanley, S. A., Raghavan, S., Hwang, W. W., & Cox, J. S. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2235593100 · Cited by 570
Self-citationGuinn, K. M., Hickey, M. J., Mathur, S. K., Zakel, K. L., Grotzke, J. E., Lewinsohn, D. M., Smith, S., & Sherman, D. R. (2004) · Molecular Microbiology · doi:10.1046/j.1365-2958.2003.03844.x · Cited by 508
Research works printed but not linked: 4
- Stanley, S. A., Raghavan, S., Hwang, W. W. & Cox, J. S. Acute infection and macrophage subversion by Mycobacterium tuberculosis require a specialized secretion system. Proc. Natl Acad. Sci. USA 100, 13001–13006 (2003) · DOI · Paper page
- MacGurn, J. A., Raghavan, S., Stanley, S. A. & Cox, J. S. A non-RD1 gene cluster is required for Snm secretion in Mycobacterium tuberculosis . Mol. Microbiol. 57, 1653–1663 (2005) · DOI · Paper page
- Greenstein, A. E. et al. tuberculosis Ser/Thr protein kinase D phosphorylates an anti-anti-sigma factor homolog. PLoS Pathog. 3, e49 (2007) · DOI
- Schnappinger, D. et al. Transcriptional adaptation of Mycobacterium tuberculosis within macrophages: Insights into the phagosomal environment. J. Exp. Med. 198, 693–704 (2003) · DOI · Paper page
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Virulence factors of the Mycobacterium tuberculosis complex
Forrellad, M. A., Klepp, L. I., Gioffré, A., y García, J. S., Morbidoni, H. R., Santangelo, M. D. L. P., Cataldi, A. A., & Bigi, F. (2013) · Virulence · doi:10.4161/viru.22329 · Cited by 676
The complex extracellular biology ofStreptomyces
Chater, K. F., Bíró, S., Lee, K. J., Palmer, T., & Schrempf, H. (2009) · FEMS Microbiology Reviews · doi:10.1111/j.1574-6976.2009.00206.x · Cited by 493
ESX secretion systems: mycobacterial evolution to counter host immunity
Gröschel, M. I., Sayes, F., Simeone, R., Majlessi, L., & Brosch, R. (2016) · Nature Reviews Microbiology · doi:10.1038/nrmicro.2016.131 · Cited by 382
Systematic Genetic Nomenclature for Type VII Secretion Systems
Bitter, W., Houben, E. N. G., Bottai, D., Brodin, P., Brown, E. J., Cox, J. S., Derbyshire, K., Fortune, S. M., Gao, L.-Y., Liu, J., et al. (2009) · PLoS Pathogens · doi:10.1371/journal.ppat.1000507 · Cited by 307
Self-citationRohde, K. H., Veiga, D. F. T., Caldwell, S., Balázsi, G., & Russell, D. G. (2012) · PLoS Pathogens · doi:10.1371/journal.ppat.1002769 · Cited by 270
Metadata
- Authors
- Raghavan, S., Manzanillo, P., Chan, K., Dovey, C., & Cox, J. S.
- Affiliations
- University of California, San Francisco (US)
- Corresponding author
- Cox, Jeffery S.
- Venue
- Nature
- Published
- 2008-08-07
- Volume
- 454
- Issue
- 7205
- Pages
- 717-721
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC2862998
- OpenAlex
- W1973827044
- Cited by
- 202
- References
- 42
- Citations by year
- 2026: 7 · 2025: 6 · 2024: 4 · 2023: 7 · 2022: 5 · 2021: 5 · 2020: 9 · 2019: 11 · 2018: 6 · 2017: 9 · 2016: 13 · 2015: 14 · 2014: 16 · 2013: 15 · 2012: 19
- FWCI
- 12.06
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- W. M. Keck Foundation
- National Institutes of Health
- National Institute of Allergy and Infectious Diseases (AI63302, AI51667, R01AI051667, P01AI063302)
- 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 › Microbiology › Escherichia coli research studies
- Keywords
- Mycobacterium tuberculosis, ESX-1 secretion system, transcriptional regulation, virulence factors, negative feedback loop, promoter activation, tuberculosis vaccine development, host-pathogen interaction
- MeSH terms
- Animals, Bacterial Proteins, Macrophages, Mice, Inbred C57BL, Mycobacterium tuberculosis, Operon, Promoter Regions, Genetic, Transcription Factors, Transcription, Genetic, Virulence, Transcriptional Activation, Gene Expression Regulation, Bacterial, Virulence Factors, Mice
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