Bacterial outer membrane vesicles mediate cytosolic localization of LPS and caspase-11 activation

By S. Vanaja, Ashley J. Russo, Bharat Behl, Ishita Banerjee, Maya P. Yankova, S. Deshmukh, Vijay A. K. Rathinam. Cell, 2016

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SUMMARY Sensing of lipopolysaccharide (LPS) in the cytosol triggers caspase-11 activation and is central to host defense against Gram-negative bacterial infections and to the pathogenesis of sepsis. Most Gram-negative bacteria that activate caspase-11 however are not cytosolic and the mechanism by which LPS from these bacteria gains access to caspase-11 in the cytosol remains elusive. Here we identify outer membrane vesicles (OMV) produced by Gram-negative bacteria as a vehicle that delivers LPS into the cytosol triggering caspase-11-dependent effector responses in vitro and in vivo. OMV are internalized via endocytosis, and LPS is released into the cytosol from early endosomes. The use of hypovesiculating bacterial mutants, compromised in their ability to generate OMV, reveal the importance of OMV in mediating the cytosolic localization of LPS. Collectively, these findings demonstrate a critical role for OMV in enabling the cytosolic entry of LPS and consequently caspase-11 activation during Gram-negative bacterial infections.

Subfields: Epidemiology, Microbiology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/09a97df65b2a7ce23a0f76733077def5b90c56c3