Mycobacterial Esx-3 Requires Multiple Components for Iron Acquisition
The type VII secretion systems are conserved across mycobacterial species and in many Gram-positive bacteria. While the well-characterized Esx-1 pathway is required for the virulence of pathogenic mycobacteria and conjugation in the model organism Mycobacterium smegmatis, Esx-3 contributes to mycoba...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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American Society for Microbiology
2014
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| Online Access: | http://hdl.handle.net/1721.1/89168 https://orcid.org/0000-0002-7203-4299 |
| _version_ | 1826202761447866368 |
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| author | Siegrist, M. Sloan Steigedal, Magnus Ahmad, Rushdy Mehra, Alka Dragset, Marte S. Schuster, Brian M. Philips, Jennifer A. Rubin, Eric J. Carr, Steven A |
| author2 | Koch Institute for Integrative Cancer Research at MIT |
| author_facet | Koch Institute for Integrative Cancer Research at MIT Siegrist, M. Sloan Steigedal, Magnus Ahmad, Rushdy Mehra, Alka Dragset, Marte S. Schuster, Brian M. Philips, Jennifer A. Rubin, Eric J. Carr, Steven A |
| author_sort | Siegrist, M. Sloan |
| collection | MIT |
| description | The type VII secretion systems are conserved across mycobacterial species and in many Gram-positive bacteria. While the well-characterized Esx-1 pathway is required for the virulence of pathogenic mycobacteria and conjugation in the model organism Mycobacterium smegmatis, Esx-3 contributes to mycobactin-mediated iron acquisition in these bacteria. Here we show that several Esx-3 components are individually required for function under low-iron conditions but that at least one, the membrane-bound protease MycP3 of M. smegmatis, is partially expendable. All of the esx-3 mutants tested, including the ΔmycP3ms mutant, failed to export the native Esx-3 substrates EsxHms and EsxGms to quantifiable levels, as determined by targeted mass spectrometry. Although we were able to restore low-iron growth to the esx-3 mutants by genetic complementation, we found a wide range of complementation levels for protein export. Indeed, minute quantities of extracellular EsxHms and EsxGms were sufficient for iron acquisition under our experimental conditions. The apparent separation of Esx-3 function in iron acquisition from robust EsxGms and EsxHms secretion in the ΔmycP3ms mutant and in some of the complemented esx-3 mutants compels reexamination of the structure-function relationships for type VII secretion systems. |
| first_indexed | 2024-09-23T12:17:47Z |
| format | Article |
| id | mit-1721.1/89168 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T12:17:47Z |
| publishDate | 2014 |
| publisher | American Society for Microbiology |
| record_format | dspace |
| spelling | mit-1721.1/891682022-10-01T08:53:56Z Mycobacterial Esx-3 Requires Multiple Components for Iron Acquisition Siegrist, M. Sloan Steigedal, Magnus Ahmad, Rushdy Mehra, Alka Dragset, Marte S. Schuster, Brian M. Philips, Jennifer A. Rubin, Eric J. Carr, Steven A Koch Institute for Integrative Cancer Research at MIT Carr, Steven A. The type VII secretion systems are conserved across mycobacterial species and in many Gram-positive bacteria. While the well-characterized Esx-1 pathway is required for the virulence of pathogenic mycobacteria and conjugation in the model organism Mycobacterium smegmatis, Esx-3 contributes to mycobactin-mediated iron acquisition in these bacteria. Here we show that several Esx-3 components are individually required for function under low-iron conditions but that at least one, the membrane-bound protease MycP3 of M. smegmatis, is partially expendable. All of the esx-3 mutants tested, including the ΔmycP3ms mutant, failed to export the native Esx-3 substrates EsxHms and EsxGms to quantifiable levels, as determined by targeted mass spectrometry. Although we were able to restore low-iron growth to the esx-3 mutants by genetic complementation, we found a wide range of complementation levels for protein export. Indeed, minute quantities of extracellular EsxHms and EsxGms were sufficient for iron acquisition under our experimental conditions. The apparent separation of Esx-3 function in iron acquisition from robust EsxGms and EsxHms secretion in the ΔmycP3ms mutant and in some of the complemented esx-3 mutants compels reexamination of the structure-function relationships for type VII secretion systems. Broad Institute of MIT and Harvard National Institutes of Health (U.S.) (NIH/NIAID grant 1P01 AI074805-01A1) National Institutes of Health (U.S.) (NIH/NIAID grant 1R01 AI087682-01A1) Doris Duke Charitable Foundation (Clinical Scientist Development Award) Research Council of Norway (grant 220836/H10) Research Council of Norway (grant 223255/F50) 2014-09-04T14:27:25Z 2014-09-04T14:27:25Z 2014-05 2014-03 Article http://purl.org/eprint/type/JournalArticle 2150-7511 http://hdl.handle.net/1721.1/89168 Siegrist, M. S., M. Steigedal, R. Ahmad, A. Mehra, M. S. Dragset, B. M. Schuster, J. A. Philips, S. A. Carr, and E. J. Rubin. “Mycobacterial Esx-3 Requires Multiple Components for Iron Acquisition.” mBio 5, no. 3 (May 6, 2014): e01073–14–e01073–14. https://orcid.org/0000-0002-7203-4299 en_US http://dx.doi.org/10.1128/mBio.01073-14 mBio Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/3.0 application/pdf American Society for Microbiology American Society for Microbiology |
| spellingShingle | Siegrist, M. Sloan Steigedal, Magnus Ahmad, Rushdy Mehra, Alka Dragset, Marte S. Schuster, Brian M. Philips, Jennifer A. Rubin, Eric J. Carr, Steven A Mycobacterial Esx-3 Requires Multiple Components for Iron Acquisition |
| title | Mycobacterial Esx-3 Requires Multiple Components for Iron Acquisition |
| title_full | Mycobacterial Esx-3 Requires Multiple Components for Iron Acquisition |
| title_fullStr | Mycobacterial Esx-3 Requires Multiple Components for Iron Acquisition |
| title_full_unstemmed | Mycobacterial Esx-3 Requires Multiple Components for Iron Acquisition |
| title_short | Mycobacterial Esx-3 Requires Multiple Components for Iron Acquisition |
| title_sort | mycobacterial esx 3 requires multiple components for iron acquisition |
| url | http://hdl.handle.net/1721.1/89168 https://orcid.org/0000-0002-7203-4299 |
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