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dc.contributor.authorAbdallah, Abdallah
dc.contributor.authorWeerdenburg, Eveline M.
dc.contributor.authorGuan, Qingtian
dc.contributor.authorUmmels, Roy
dc.contributor.authorBorggreve, Stephanie
dc.contributor.authorAdroub, Sabir
dc.contributor.authorMalas, Tareq Majed Yasin
dc.contributor.authorNaeem, Raeece
dc.contributor.authorZhang, Huoming
dc.contributor.authorOtto, Thomas D.
dc.contributor.authorBitter, Wilbert
dc.contributor.authorPain, Arnab
dc.date.accessioned2019-02-14T08:20:42Z
dc.date.available2019-02-14T08:20:42Z
dc.date.issued2019-01-23
dc.identifier.citationAbdallah AM, Weerdenburg EM, Guan Q, Ummels R, Borggreve S, et al. (2019) Integrated transcriptomic and proteomic analysis of pathogenic mycobacteria and their esx-1 mutants reveal secretion-dependent regulation of ESX-1 substrates and WhiB6 as a transcriptional regulator. PLOS ONE 14: e0211003. Available: http://dx.doi.org/10.1371/journal.pone.0211003.
dc.identifier.issn1932-6203
dc.identifier.doi10.1371/journal.pone.0211003
dc.identifier.urihttp://hdl.handle.net/10754/631047
dc.description.abstractThe mycobacterial type VII secretion system ESX-1 is responsible for the secretion of a number of proteins that play important roles during host infection. The regulation of the expression of secreted proteins is often essential to establish successful infection. Using transcriptome sequencing, we found that the abrogation of ESX-1 function in Mycobacterium marinum leads to a pronounced increase in gene expression levels of the espA operon during the infection of macrophages. In addition, the disruption of ESX-1-mediated protein secretion also leads to a specific down-regulation of the ESX-1 substrates, but not of the structural components of this system, during growth in culture medium. This effect is observed in both M. marinum and M. tuberculosis. We established that down-regulation of ESX-1 substrates is the result of a regulatory process that is influenced by the putative transcriptional regulator whib6, which is located adjacent to the esx-1 locus. In addition, the overexpression of the ESX-1-associated PE35/PPE68 protein pair resulted in a significantly increased secretion of the ESX-1 substrate EsxA, demonstrating a functional link between these proteins. Taken together, these data show that WhiB6 is required for the secretion-dependent regulation of ESX-1 substrates and that ESX-1 substrates are regulated independently from the structural components, both during infection and as a result of active secretion.
dc.description.sponsorshipAcknowledgments: We thank Astrid van der Sar and Esther Stoop for providing the M. marinum E11 ESX-1 mutants. The authors thank members of the Bioscience Core Lab (BCL) at KAUST for sequencing the RNA-seq libraries on the Illumina Hiseq platform and for running protein samples through the quantitative proteomics workflow with the LTQ-Orbitrap Velos instrument (Thermo Scientific). Funding: Work in AP’s laboratory is supported by the KAUST faculty baseline fund (BAS/1/1020-01-01).
dc.publisherPublic Library of Science (PLoS)
dc.relation.urlhttps://journals.plos.org/plosone/article?id=10.1371/journal.pone.0211003
dc.rightsThis is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.titleIntegrated transcriptomic and proteomic analysis of pathogenic mycobacteria and their esx-1 mutants reveal secretion-dependent regulation of ESX-1 substrates and WhiB6 as a transcriptional regulator
dc.typeArticle
dc.contributor.departmentBiological and Environmental Sciences and Engineering (BESE) Division
dc.contributor.departmentBioscience Core Lab
dc.contributor.departmentBioscience Program
dc.contributor.departmentComputer Science Program
dc.contributor.departmentComputer, Electrical and Mathematical Sciences and Engineering (CEMSE) Division
dc.contributor.departmentNGS, qPCR and Single Cell Genomics
dc.contributor.departmentPathogen Genomics Laboratory
dc.contributor.departmentProteomics and Protein Expression
dc.contributor.departmentR&F Operations
dc.identifier.journalPLOS ONE
dc.eprint.versionPublisher's Version/PDF
dc.contributor.institutionDepartment of Medical Microbiology and Infection Control, VU University Medical Center, Amsterdam, The Netherlands.
dc.contributor.institutionPathogen Genomics, The Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom.
kaust.personAbdallah, Abdallah
kaust.personGuan, Qingtian
kaust.personAdroub, Sabir
kaust.personMalas, Tareq Majed Yasin
kaust.personNaeem, Raeece
kaust.personZhang, Huoming
kaust.personPain, Arnab
kaust.grant.numberBAS/1/1020-01-01
dc.relation.issupplementedbybioproject:PRJEB8560
refterms.dateFOA2019-02-14T09:07:49Z
display.relations<b>Is Supplemented By:</b><br/> <ul><li><i>[Bioproject]</i> <br/> Title: A genomic sequence and expression diversity catalogue of BCGPublication Date: 2015-09-01. bioproject: <a href="https://www.ncbi.nlm.nih.gov/bioproject/?term=PRJEB8560" >PRJEB8560</a> Handle: <a href="http://hdl.handle.net/10754/666454" >10754/666454</a></a></li></ul>


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This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Except where otherwise noted, this item's license is described as This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.