Open AccessESX‐1‐mediated translocation to the cytosol controls virulence of mycobacteria
Author(s) -
Houben Diane,
Demangel Caroline,
van Ingen Jakko,
Perez Jorge,
Baldeón Lucy,
Abdallah Abdallah M.,
Caleechurn Laxmee,
Bottai Daria,
van Zon Maaike,
de Punder Karin,
van der Laan Tridia,
Kant Arie,
Bossersde Vries Ruth,
Willemsen Peter,
Bitter Wilbert,
van Soolingen Dick,
Brosch Roland,
van der Wel Nicole,
Peters Peter J.
Publication year - 2012
Publication title -
cellular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.542
H-Index - 138
eISSN - 1462-5822
pISSN - 1462-5814
DOI - 10.1111/j.1462-5822.2012.01799.x
Subject(s) - virulence , biology , chromosomal translocation , microbiology and biotechnology , secretion , cytosol , mycobacterium , mycobacterium tuberculosis , phagolysosome , esat 6 , phagosome , tuberculosis , bacteria , phagocytosis , genetics , gene , biochemistry , bacterial protein , enzyme , medicine , pathology
Summary 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.