RT Journal Article SR Electronic(1) A1 Cadieux, Nathalie A1 Parra, Marcela A1 Cohen, Hannah A1 Maric, Dragan A1 Morris, Sheldon L. A1 Brennan, Michael J.YR 2011 T1 Induction of cell death after localization to the host cell mitochondria by the Mycobacterium tuberculosis PE_PGRS33 protein JF Microbiology, VO 157 IS 3 SP 793 OP 804 DO https://doi.org/10.1099/mic.0.041996-0 PB Microbiology Society, SN 1465-2080, AB 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., UL https://www.microbiologyresearch.org/content/journal/micro/10.1099/mic.0.041996-0