%0 Journal Article %A Cadieux, Nathalie %A Parra, Marcela %A Cohen, Hannah %A Maric, Dragan %A Morris, Sheldon L. %A Brennan, Michael J. %T Induction of cell death after localization to the host cell mitochondria by the Mycobacterium tuberculosis PE_PGRS33 protein %D 2011 %J Microbiology, %V 157 %N 3 %P 793-804 %@ 1465-2080 %R https://doi.org/10.1099/mic.0.041996-0 %K RD, human rhabdomyosarcoma %K BMMO, bone marrow-derived macrophages %K mAb, monoclonal antibody %K IFA, immunofluorescence assay %K PI, propidium iodide %I Microbiology Society, %X PE_PGRS33 is the most studied member of the unique PE family of mycobacterial proteins. These proteins are composed of a PE domain (Pro–Glu motif), a linker region and a PGRS domain (polymorphic GC-rich-repetitive sequence). Previous studies have shown that PE_PGRS33 is surface-exposed, constitutively expressed during growth and infection, involved in creating antigenic diversity, and able to induce death in transfected or infected eukaryotic cells. In this study, we showed that PE_PGRS33 co-localizes to the mitochondria of transfected cells, a phenomenon dependent on the linker region and the PGRS domain, but not the PE domain. Using different genetic fusions and chimeras, we also demonstrated a direct correlation between localization to the host mitochondria and the induction of cell death. Finally, although all constructs localizing to the mitochondria did induce apoptosis, only the wild-type PE_PGRS33 with its own PE domain also induced primary necrosis, indicating a potentially important role for the PE domain. Considering the importance of primary necrosis in Mycobacterium tuberculosis dissemination during natural infection, the PE_PGRS33 protein may play a crucial role in the pathogenesis of tuberculosis. %U https://www.microbiologyresearch.org/content/journal/micro/10.1099/mic.0.041996-0