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bioRxiv · 10.1101/2021.09.06.459093

Legionella pneumophila regulates host cell motility by targeting Phldb2 with a 14-3-3ζ-dependent protease effector

Song, L.·Luo, J.·Huang, D.·Tan, Y.·Liu, Y.·Yu, K.·Zhang, Y.·Liu, X.·Li, D.·Luo, Z.-Q.
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Abstract

The cytoskeleton network of eukaryotic cells is essential for diverse cellular processes, including vesicle trafficking, cell motility and immunity, thus is a common target for bacterial virulence factors. A number of effectors from the bacterial pathogen Legionella pneumophila have been shown to modulate the function of host actin cytoskeleton to construct the Legionella-containing vacuole (LCV) permissive for its intracellular replication. In this study, we identified the Dot/Icm effector Lem8 (Lpg1290) as a protease that interferes with host motility. We show that the protease activity of Lem8 is catalyzed by a Cys-His-Asp motif known to be associated with diverse biochemical activities. Intriguingly, we found that Lem8 interacts with the host regulatory protein 14-3-3{zeta}, which activates its protease activity. Furthermore, Lem8 undergoes self-cleavage in a process that requires 14-3-3{zeta}. We identified the PH domain-containing protein Phldb2 involved in cell migration as a target of Lem8 and demonstrate that Lem8 plays a role in the inhibition of host cell migration. Our results reveal a novel mechanism of inhibiting host cell motility by L. pneumophila for its virulence.

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Song, L., Luo, J., Huang, D., Tan, Y., Liu, Y., Yu, K., Zhang, Y., Liu, X., Li, D., Luo, Z.-Q.. 2021-09-06. Legionella pneumophila regulates host cell motility by targeting Phldb2 with a 14-3-3ζ-dependent protease effector. https://doi.org/10.1101/2021.09.06.459093

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