文献类型：期刊文献

英文题名：Salt-Inducing Assembly Polymorphism Strategy for Cytotoxicity Differentiation of Phenol-Soluble Modulin α3 Assemblies

作者：Xuan, Qize[1];He, Jiaxin[1];Zhang, Wenxue[1];Zhang, Wei[1];Zhang, Qi[1];Zhou, Yao[1];Wei, Anqi[1];Wang, Hao[2];Li, Hui[3];Chen, Chao[1,3];Wang, Ping[4]

机构：[1]East China Univ Sci & Technol, Biomed Nanotechnol Ctr, Shanghai Collaborat Innovat Ctr Biomfg Technol, Sch Biotechnol,State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[2]Shanghai Jiao Tong Univ, Shanghai Gen Hosp, Dept Obstet & Gynecol, Sch Med, Shanghai 200080, Peoples R China;[3]Shanghai Univ, Inst Environm Pollut & Hlth, Sch Environm & Chem Engn, Shanghai 200444, Peoples R China;[4]Univ Minnesota, Dept Bioprod & Biosyst Engn, St Paul, MN 55108 USA

年份：2022

卷号：23

期号：8

起止页码：3318

外文期刊名：BIOMACROMOLECULES

收录：;EI(收录号：20223412588344);WOS:【SCI-EXPANDED(收录号:WOS:000831960300001)】；

基金：This work was sponsored by the National Natural Science Foundation of China (nos. 21908059 and 21636003) , the China Postdoctoral Science Foundation (no. 2019M651419) , the Shanghai Sailing Program (nos. 19YF1410900 and 21YF1451700) , the Natural Science Foundation of Shanghai (22ZR1415400) , the Fundamental Research Funds for the Central Universities (no. 22221818014) , the Shanghai Postdoctoral Excellence Program (no. 2018011) , the Foundation of State Key Laboratory of Biobased Material and Green Papermaking, Qilu University of Technology, Shandong Academy of Sciences (grant no: GZKF202031) , and the Open Funding Project of the State Key Laboratory of Bioreactor Engineering.

语种：英文

外文关键词：Bacteria - Cytotoxicity - Polymorphism

摘要：Phenol-soluble modulin alpha 3 (PSM alpha 3) can self-assemble into fibrous assemblies with a unique "cross-alpha" sheet structure, which serves as a key virulence factor in the infection of Staphylococcus aureus. However, the structure-cytotoxicity relationships of PSM alpha 3 still remain elusive. Herein, we utilized the strategy of salt-inducing assembly polymorphism to controllably prepare three PSM alpha 3 assemblies with morphological and structural distinctions, including amorphous aggregates (AAs), rigid fibrils (RFs), and oligomers/curvilinear fibrils (OCFs), which provided a convincing method to facilitate the structure-cytotoxicity investigation of PSM alpha 3 assemblies. Our results affirmed that amyloid fibrillation was essential for the enhancement of PSMa3 cytotoxicity, which was proved based on the evidence that RFs and OCFs both triggered more obvious cytotoxicity than AAs. Furthermore, our study also demonstrated that the cytotoxicity was severely dependent on the size and structure of PSM alpha 3 fibrils. In detail, smaller OCFs rich in alpha-helices exhibited stronger virulence than RFs with larger sizes and low alpha-helical contents. The cytotoxicity caused by such fibrils was achieved via a membrane-disrupting mechanism, in which RFs and OCFs might be prone to membrane thinning and perforation, respectively. This strategy of salt-inducing PSM alpha 3 assembly polymorphism facilitated the comprehension of the relationship between the characteristics of PSM alpha 3 assemblies and their cytotoxicity and was also helpful to understanding the intrinsic assembly mechanism of the PSM alpha 3.