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<i>Mycobacterium tuberculosis</i> (Mtb) is the causative agent of
tuberculosis. Its success as a pathogen is dependent on an arsenal of
secreted virulence factors which target host cell organelles. In this
report, we have characterized the effects of two proteins known to be
secreted by Mtb on eukaryotic mitochondria: ESAT-6 and a member of the
poorly-described PE/PPE protein family, PE17. Intracellular expression
of ESAT-6 in A549 cells did not induce mitochondrial fragmentation. In
contrast, expression of PE17 caused extensive mitochondrial
fragmentation and an overall reduction in mass. Further characterization
of the effects of PE17 within host cells revealed a dramatic decrease in
the mass of the trans-Golgi network and the Golgi stack with lesser but
significant decreases in late endosomes and lysosomes. The endoplasmic
reticulum and organelles of the early endocytic pathway were not
significantly affected. PE17 specifically colocalized with large,
cytoplasmic lipid droplets via a C-terminal domain, suggesting a
significant role for PE17 in the disruption of multiple host cell
organelles and a novel interaction with host lipid droplets.</div>