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dc.contributor.authorAbdallah, Abdallah
dc.contributor.authorWeerdenburg, Eveline
dc.contributor.authorGuan, Qingtian
dc.contributor.authorUmmels, Roy
dc.contributor.authorBorggreve, S
dc.contributor.authorAdroub, Sabir
dc.contributor.authorMalas, Tareq Majed Yasin
dc.contributor.authorNaeem, Raeece
dc.contributor.authorZhang, Huoming
dc.contributor.authorOtto, Thomas
dc.contributor.authorBitter, Wilbert
dc.contributor.authorPain, Arnab
dc.date.accessioned2018-05-31T06:38:47Z
dc.date.available2018-05-31T06:38:47Z
dc.date.issued2018-04-09
dc.identifier.citationAbdallah AM, Weerdenburg E, Guan Q, Ummels R, Borggreve S, et al. (2018) WhiB6 is required for the secretion-dependent regulation of ESX-1 substrates in pathogenic mycobacteria. Available: http://dx.doi.org/10.1101/297440.
dc.identifier.doi10.1101/297440
dc.identifier.urihttp://hdl.handle.net/10754/628004
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, suggesting an important role in ESX-1-mediated virulence during the early phase of infection. 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.sponsorshipWe thank Astrid van der Sar and Esther Stoop for providing the M. marinum E11 ESX-1 mutants. Work in AP’s laboratory is supported by the KAUST faculty baseline fund (BAS/1/1020-01-01). 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).
dc.publisherCold Spring Harbor Laboratory
dc.relation.urlhttps://www.biorxiv.org/content/early/2018/05/02/297440
dc.rightsArchived with thanks to BioRxiv
dc.titleWhiB6 is required for the secretion-dependent regulation of ESX-1 substrates in pathogenic mycobacteria.
dc.typePreprint
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.departmentNGS, qPCR and Single Cell Genomics
dc.contributor.departmentPathogen Genomics Laboratory
dc.contributor.departmentProteomics and Protein Expression
dc.eprint.versionPre-print
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
refterms.dateFOA2018-06-14T06:41:21Z


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