Published 8 December 2003. doi:10.1083/jcb1635iti4
© The Rockefeller University Press,
0021-9525/2003/12/927 $8.00
The Journal of Cell Biology, Volume 163, Number 5, 927-927
Fusion fuels killing
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Macrophages infected by Salmonella accumulate vesicles that resemble autophagosomes.
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On page 1123, Hernandez et al. demonstrate that a human bacterial pathogen makes host defense cells self-destruct by engulfing their own organelles.
This engulfment, known as autophagy, is commonly used by eukaryotic cells to remove damaged organelles by enveloping them in membranes (probably derived from the ER) that later fuse with lysosomes. High levels of autophagy is also a form of programmed cell death—a process that the bacterium Salmonella is now shown to hijack.
The authors show that the Salmonella protein SipB is all the bacteria need to get autophagy rolling. SipB is a translocase that sends pathogenic effector proteins into host cells. The authors show that SipB also functions within the infected cell, where it finds its way to mitochondria. There, SipB's demonstrated fusion activity may explain the appearance of damaged and bloated mitochondria, which then become a target for the autophagic apparatus. The end results, visualized by the group, were multimembranous structures that resemble authophagic vesicles, contain mitochondrial and ER proteins, and occasionally surround entire mitochondria.
Salmonella can also kill macrophages through a faster necrosis-like pathway that, unlike autophagy, depends on caspase-1 activity. The two killing methods may result in different immunological responses from the host, but as yet it is not even clear whether macrophage death is a benefit for the host (by halting bacterial replication) or the pathogen (by impairing defense responses). 
Nicole LeBrasseur
lebrasn{at}rockefeller.edu
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