ESX-1-mediated translocation to the cytosol controls virulence of mycobacteria

Handle URI:
http://hdl.handle.net/10754/565974
Title:
ESX-1-mediated translocation to the cytosol controls virulence of mycobacteria
Authors:
Houben, Diane; Demangel, Caroline; Van Ingen, Jakko; Perez, Jorge; Baldeón, Lucy R.; Abdallah, Abdallah; Caleechurn, Laxmee; Bottai, Daria; Van Zon, Maaike; De Punder, Karin; Van Der Laan, Tridia; Kant, Arie; Bossers-De Vries, Ruth; Willemsen, Peter Th J; Bitter, Wilbert M.; Van Soolingen, Dick; Brosch, Roland; Van Der Wel, Nicole N.; Peters, Peter J.
Abstract:
Mycobacterium species, including Mycobacterium tuberculosis and Mycobacterium leprae, are among the most potent human bacterial pathogens. The discovery of cytosolic mycobacteria challenged the paradigm that these pathogens exclusively localize within the phagosome of host cells. As yet the biological relevance of mycobacterial translocation to the cytosol remained unclear. In this current study we used electron microscopy techniques to establish a clear link between translocation and mycobacterial virulence. Pathogenic, patient-derived mycobacteria species were found to translocate to the cytosol, while non-pathogenic species did not. We were further able to link cytosolic translocation with pathogenicity by introducing the ESX-1 (type VII) secretion system into the non-virulent, exclusively phagolysosomal Mycobacterium bovis BCG. Furthermore, we show that translocation is dependent on the C-terminus of the early-secreted antigen ESAT-6. The C-terminal truncation of ESAT-6 was shown to result in attenuation in mice, again linking translocation to virulence. Together, these data demonstrate the molecular mechanism facilitating translocation of mycobacteria. The ability to translocate from the phagolysosome to the cytosol is with this study proven to be biologically significant as it determines mycobacterial virulence. © 2012 Blackwell Publishing Ltd.
KAUST Department:
Biological and Environmental Sciences and Engineering (BESE) Division
Publisher:
Wiley-Blackwell
Journal:
Cellular Microbiology
Issue Date:
8-May-2012
DOI:
10.1111/j.1462-5822.2012.01799.x
PubMed ID:
22524898
Type:
Article
ISSN:
14625814
Appears in Collections:
Articles; Biological and Environmental Sciences and Engineering (BESE) Division

Full metadata record

DC FieldValue Language
dc.contributor.authorHouben, Dianeen
dc.contributor.authorDemangel, Carolineen
dc.contributor.authorVan Ingen, Jakkoen
dc.contributor.authorPerez, Jorgeen
dc.contributor.authorBaldeón, Lucy R.en
dc.contributor.authorAbdallah, Abdallahen
dc.contributor.authorCaleechurn, Laxmeeen
dc.contributor.authorBottai, Dariaen
dc.contributor.authorVan Zon, Maaikeen
dc.contributor.authorDe Punder, Karinen
dc.contributor.authorVan Der Laan, Tridiaen
dc.contributor.authorKant, Arieen
dc.contributor.authorBossers-De Vries, Ruthen
dc.contributor.authorWillemsen, Peter Th Jen
dc.contributor.authorBitter, Wilbert M.en
dc.contributor.authorVan Soolingen, Dicken
dc.contributor.authorBrosch, Rolanden
dc.contributor.authorVan Der Wel, Nicole N.en
dc.contributor.authorPeters, Peter J.en
dc.date.accessioned2015-08-12T08:57:39Zen
dc.date.available2015-08-12T08:57:39Zen
dc.date.issued2012-05-08en
dc.identifier.issn14625814en
dc.identifier.pmid22524898en
dc.identifier.doi10.1111/j.1462-5822.2012.01799.xen
dc.identifier.urihttp://hdl.handle.net/10754/565974en
dc.description.abstractMycobacterium species, including Mycobacterium tuberculosis and Mycobacterium leprae, are among the most potent human bacterial pathogens. The discovery of cytosolic mycobacteria challenged the paradigm that these pathogens exclusively localize within the phagosome of host cells. As yet the biological relevance of mycobacterial translocation to the cytosol remained unclear. In this current study we used electron microscopy techniques to establish a clear link between translocation and mycobacterial virulence. Pathogenic, patient-derived mycobacteria species were found to translocate to the cytosol, while non-pathogenic species did not. We were further able to link cytosolic translocation with pathogenicity by introducing the ESX-1 (type VII) secretion system into the non-virulent, exclusively phagolysosomal Mycobacterium bovis BCG. Furthermore, we show that translocation is dependent on the C-terminus of the early-secreted antigen ESAT-6. The C-terminal truncation of ESAT-6 was shown to result in attenuation in mice, again linking translocation to virulence. Together, these data demonstrate the molecular mechanism facilitating translocation of mycobacteria. The ability to translocate from the phagolysosome to the cytosol is with this study proven to be biologically significant as it determines mycobacterial virulence. © 2012 Blackwell Publishing Ltd.en
dc.publisherWiley-Blackwellen
dc.titleESX-1-mediated translocation to the cytosol controls virulence of mycobacteriaen
dc.typeArticleen
dc.contributor.departmentBiological and Environmental Sciences and Engineering (BESE) Divisionen
dc.identifier.journalCellular Microbiologyen
kaust.authorAbdallah, Abdallahen
kaust.authorBossers-De Vries, Ruthen
kaust.authorWillemsen, Peter Th Jen

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