Chlamydia-induced curvature of the host-cell plasma membrane is required for infection.

Hänsch, Sebastian; Spona, Dominik; Murra, Gido; Köhrer, Karl; Subtil, Agathe; Furtado, Ana Rita; Lichtenthaler, Stephan F; Dislich, Bastian; Mölleken, Katja; Hegemann, Johannes H (2020). Chlamydia-induced curvature of the host-cell plasma membrane is required for infection. Proceedings of the National Academy of Sciences of the United States of America - PNAS, 117(5), pp. 2634-2644. National Academy of Sciences NAS 10.1073/pnas.1911528117

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During invasion of host cells, Chlamydia pneumoniae secretes the effector protein CPn0678, which facilitates internalization of the pathogen by remodeling the target cell's plasma membrane and recruiting sorting nexin 9 (SNX9), a central multifunctional endocytic scaffold protein. We show here that the strongly amphipathic N-terminal helix of CPn0678 mediates binding to phospholipids in both the plasma membrane and synthetic membranes, and is sufficient to induce extensive membrane tubulations. CPn0678 interacts via its conserved C-terminal polyproline sequence with the Src homology 3 domain of SNX9. Thus, SNX9 is found at bacterial entry sites, where C. pneumoniae is internalized via EGFR-mediated endocytosis. Moreover, depletion of human SNX9 significantly reduces internalization, whereas ectopic overexpression of CPn0678-GFP results in a dominant-negative effect on endocytotic processes in general, leading to the uptake of fewer chlamydial elementary bodies and diminished turnover of EGFR. Thus, CPn0678 is an early effector involved in regulating the endocytosis of C. pneumoniae in an EGFR- and SNX9-dependent manner.

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