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Interaction of Mycobacterium tuberculosis Virulence Factor RipA with Chaperone MoxR1 Is Required for Transport through the TAT Secretion System
Mycobacterium tuberculosis is a leading cause of death worldwide. The M. tuberculosis TAT (twin-arginine translocation) protein secretion system is present at the cytoplasmic membrane of mycobacteria and is known to transport folded proteins. The TAT secretion system is reported to be essential for...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society of Microbiology
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4810496/ https://www.ncbi.nlm.nih.gov/pubmed/26933057 http://dx.doi.org/10.1128/mBio.02259-15 |
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author | Bhuwan, Manish Arora, Naresh Sharma, Ashish Khubaib, Mohd Pandey, Saurabh Chaudhuri, Tapan Kumar Hasnain, Seyed Ehtesham Ehtesham, Nasreen Zafar |
author_facet | Bhuwan, Manish Arora, Naresh Sharma, Ashish Khubaib, Mohd Pandey, Saurabh Chaudhuri, Tapan Kumar Hasnain, Seyed Ehtesham Ehtesham, Nasreen Zafar |
author_sort | Bhuwan, Manish |
collection | PubMed |
description | Mycobacterium tuberculosis is a leading cause of death worldwide. The M. tuberculosis TAT (twin-arginine translocation) protein secretion system is present at the cytoplasmic membrane of mycobacteria and is known to transport folded proteins. The TAT secretion system is reported to be essential for many important bacterial processes that include cell wall biosynthesis. The M. tuberculosis secretion and invasion protein RipA has endopeptidase activity and interacts with one of the resuscitation antigens (RpfB) that are expressed during pathogen reactivation. MoxR1, a member of the ATPase family that is associated with various cellular activities, was predicted to interact with RipA based on in silico analyses. A bimolecular fluorescence complementation (BiFC) assay confirmed the interaction of these two proteins in HEK293T cells. The overexpression of RipA in Mycobacterium smegmatis and copurification with MoxR1 further validated their interaction in vivo. Recombinant MoxR1 protein, expressed in Escherichia coli, displays ATP-enhanced chaperone activity. Secretion of recombinant RipA (rRipA) protein into the E. coli culture filtrate was not observed in the absence of RipA-MoxR interaction. Inhibition of this export system in M. tuberculosis, including the key players, will prevent localization of peptidoglycan hydrolase and result in sensitivity to existing β-lactam antibiotics, opening up new candidates for drug repurposing. |
format | Online Article Text |
id | pubmed-4810496 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | American Society of Microbiology |
record_format | MEDLINE/PubMed |
spelling | pubmed-48104962016-04-04 Interaction of Mycobacterium tuberculosis Virulence Factor RipA with Chaperone MoxR1 Is Required for Transport through the TAT Secretion System Bhuwan, Manish Arora, Naresh Sharma, Ashish Khubaib, Mohd Pandey, Saurabh Chaudhuri, Tapan Kumar Hasnain, Seyed Ehtesham Ehtesham, Nasreen Zafar mBio Research Article Mycobacterium tuberculosis is a leading cause of death worldwide. The M. tuberculosis TAT (twin-arginine translocation) protein secretion system is present at the cytoplasmic membrane of mycobacteria and is known to transport folded proteins. The TAT secretion system is reported to be essential for many important bacterial processes that include cell wall biosynthesis. The M. tuberculosis secretion and invasion protein RipA has endopeptidase activity and interacts with one of the resuscitation antigens (RpfB) that are expressed during pathogen reactivation. MoxR1, a member of the ATPase family that is associated with various cellular activities, was predicted to interact with RipA based on in silico analyses. A bimolecular fluorescence complementation (BiFC) assay confirmed the interaction of these two proteins in HEK293T cells. The overexpression of RipA in Mycobacterium smegmatis and copurification with MoxR1 further validated their interaction in vivo. Recombinant MoxR1 protein, expressed in Escherichia coli, displays ATP-enhanced chaperone activity. Secretion of recombinant RipA (rRipA) protein into the E. coli culture filtrate was not observed in the absence of RipA-MoxR interaction. Inhibition of this export system in M. tuberculosis, including the key players, will prevent localization of peptidoglycan hydrolase and result in sensitivity to existing β-lactam antibiotics, opening up new candidates for drug repurposing. American Society of Microbiology 2016-03-01 /pmc/articles/PMC4810496/ /pubmed/26933057 http://dx.doi.org/10.1128/mBio.02259-15 Text en Copyright © 2016 Bhuwan et al. http://creativecommons.org/licenses/by-nc-sa/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-ShareAlike 3.0 Unported license (http://creativecommons.org/licenses/by-nc-sa/3.0/) , which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Bhuwan, Manish Arora, Naresh Sharma, Ashish Khubaib, Mohd Pandey, Saurabh Chaudhuri, Tapan Kumar Hasnain, Seyed Ehtesham Ehtesham, Nasreen Zafar Interaction of Mycobacterium tuberculosis Virulence Factor RipA with Chaperone MoxR1 Is Required for Transport through the TAT Secretion System |
title | Interaction of Mycobacterium tuberculosis Virulence Factor RipA with Chaperone MoxR1 Is Required for Transport through the TAT Secretion System |
title_full | Interaction of Mycobacterium tuberculosis Virulence Factor RipA with Chaperone MoxR1 Is Required for Transport through the TAT Secretion System |
title_fullStr | Interaction of Mycobacterium tuberculosis Virulence Factor RipA with Chaperone MoxR1 Is Required for Transport through the TAT Secretion System |
title_full_unstemmed | Interaction of Mycobacterium tuberculosis Virulence Factor RipA with Chaperone MoxR1 Is Required for Transport through the TAT Secretion System |
title_short | Interaction of Mycobacterium tuberculosis Virulence Factor RipA with Chaperone MoxR1 Is Required for Transport through the TAT Secretion System |
title_sort | interaction of mycobacterium tuberculosis virulence factor ripa with chaperone moxr1 is required for transport through the tat secretion system |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4810496/ https://www.ncbi.nlm.nih.gov/pubmed/26933057 http://dx.doi.org/10.1128/mBio.02259-15 |
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