猪链球菌2型(Streptococcus suis serotype 2,SS2)是诱发细菌性脑膜炎的一种人畜共患病原菌,宿主脑微血管内皮细胞(BMEC)是构成血脑屏障(blood-brain barrier,BBB)的主要细胞,也是病原攻击的重要靶细胞.近年发现宿主细胞核糖体蛋白SA(ribosomal protein SA,RPSA)参与SS2诱发的脑膜炎发病过程,但相关机制仍知之甚少.本研究通过对人脑微血管内皮细胞(human cortical microvessels endothelial cells/D3,HCMEC/D3)RPSA 蛋白进行序列分析、相分离能力测定,初步研究了 RPSA在SS2感染过程中的作用和机制.结果显示,HCMEC/D3 RPSA具有典型的内部无序区(IDRs)结构域;SS2感染能够诱导RPSA发生相分离,相分离显著增强了细菌对细胞的黏附能力;SS2毒力因子ENO既能够促进RPSA发生相分离,也介导了细菌与细胞的黏附.另外,SS2感染后胞内Ca2+水平升高是促进相分离的关键因素.综上,本研究证实SS2通过提升胞内Ca2+水平,促进RPSA发生相分离,从而增强SS2(ENO)与RPSA的相互作用,导致黏附并进一步引起细胞损伤造成宿主感染.本研究为SS2诱发脑膜炎的认知提供了新思路.
Streptococcus suis type 2 promotes its adhesion to cells by inducing phase separa-tion of RPSA in human brain microvascular endothelial cells
Streptococcus suis serotype 2(SS2)is a zoonotic pathogen that induces bacterial meningi-tis,and the host brain microvascular endothelial cells(BMECs)are the main cells that constitute the blood-brain barrier(BBB)and are important target cells for bacterial pathogenesis.In recent years,it has been found that host cell ribosomal protein SA(RPSA)is involved in the pathogene-sis of SS2 meningitis,but the relevant mechanism is still poorly understood.In this study,the role and mechanism of RPSA in SS2 infection were initially investigated through the sequence analysis and determination of phase separation ability of human cortical microvascular endothelial cells(HCMEC/D3).The results showed that HCMEC/D3 RPSA contains typical internal disorder re-gions(IDRs),SS2 infection induced phase separation of RPSA,which significantly enhanced the adhesion ability of bacteria to cells,and the virulence factor ENO of SS2 not only promotes the phase separation of RPSA,but also mediates bacterial adhesion to cells.In addition,elevated Ca2+levels after SS2 infection were found to be a key factor in promoting phase separation.This study confirmed that SS2 increased the level of intracellular Ca2+and promoted RPSA phase separation,thereby enhancing the interaction between SS2(ENO)and RPSA,leading to adhesion and further causing cell damage and host infection,which provided a new idea for the cognition of SS2 meningi-tis.
Streptococcus suis serotype 2ribosomal protein SAphase transitionenolaseCa2+
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