Enolase of Streptococcus suis serotype 2 promotes biomolecular condensation of ribosomal protein SA for HBMECs apoptosis.

Hexiang Jiang, Yi Sun, Fengyang Li, Xibing Yu, Siyu Lei, Sulan Du, Tong Wu, Xuan Jiang, Junhui Zhu, Jun Wang, Yalu Ji, Na Li, Xin Feng, Jingmin Gu, Wenyu Han, Lei Zeng, Liancheng Lei

BMC biology 2024 Feb 08

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Ribosomal protein SA (RPSA) of human brain microvascular endothelial cells (HBMECs) can transfer from the cytosol to the cell surface and act as a receptor for some pathogens, including Streptococcus suis serotype 2 (SS2), a zoonotic pathogen causing meningitis in pigs and humans. We previously reported that SS2 virulence factor enolase (ENO) binds to RPSA on the cell surface of HBMECs and induces apoptosis. However, the mechanism that activates RPSA translocation to the cell surface and induces ENO-mediated HBMEC apoptosis is unclear. Here, we show that RPSA localization and condensation on the host cell surface depend on its internally disordered region (IDR). ENO binds to the IDR of RPSA and promotes its interaction with RPSA and vimentin (VIM), which is significantly suppressed after 1,6-Hexanediol (1,6-Hex, a widely used tool to disrupt phase separation) treatment, indicating that ENO incorporation and thus the concentration of RPSA/VIM complexes via co-condensation. Furthermore, increasing intracellular calcium ions (Ca2+) in response to SS2 infection further facilitates the liquid-like condensation of RPSA and aggravates ENO-induced HBMEC cell apoptosis. Together, our study provides a previously underappreciated molecular mechanism illuminating that ENO-induced RPSA condensation activates the migration of RPSA to the bacterial cell surface and stimulates SS2-infected HBMEC death and, potentially, disease progression. This study offers a fresh avenue for investigation into the mechanism by which other harmful bacteria infect hosts via cell surfaces' RPSA. © 2024. The Author(s).

Citation

Hexiang Jiang, Yi Sun, Fengyang Li, Xibing Yu, Siyu Lei, Sulan Du, Tong Wu, Xuan Jiang, Junhui Zhu, Jun Wang, Yalu Ji, Na Li, Xin Feng, Jingmin Gu, Wenyu Han, Lei Zeng, Liancheng Lei. Enolase of Streptococcus suis serotype 2 promotes biomolecular condensation of ribosomal protein SA for HBMECs apoptosis. BMC biology. 2024 Feb 08;22(1):33