ARF6 promotes Streptococcus suis suilysin induced apoptosis in HBMECs

Changsheng Jiang; Pei Zhou; Xiaoqian Zhang; NingNing Ma; Yaofang Hu; Mengjia Zhang; Ahmed H Ghonaim; Huimin Li; Ling Dong; Wei Zeng; Chang Li; Yifei Lang; Yumei Sun; Qigai He; Wentao Li

doi:10.1016/j.ijbiomac.2024.131839

ARF6 promotes Streptococcus suis suilysin induced apoptosis in HBMECs

Int J Biol Macromol. 2024 Apr 23;268(Pt 2):131839. doi: 10.1016/j.ijbiomac.2024.131839. Online ahead of print.

Authors

Changsheng Jiang¹, Pei Zhou¹, Xiaoqian Zhang², NingNing Ma¹, Yaofang Hu¹, Mengjia Zhang¹, Ahmed H Ghonaim³, Huimin Li¹, Ling Dong¹, Wei Zeng⁴, Chang Li⁵, Yifei Lang⁶, Yumei Sun¹, Qigai He⁷, Wentao Li⁸

Affiliations

¹ National Key Laboratory of Agricultural Microbiology, College of Animal Sciences and Veterinary Medicine, Huazhong Agricultural University, The Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070, China.
² China Institute of Veterinary Drug Control, Beijing 102629, China.
³ National Key Laboratory of Agricultural Microbiology, College of Animal Sciences and Veterinary Medicine, Huazhong Agricultural University, The Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070, China; Desert Research Center, Cairo 11435, Egypt.
⁴ Hubei Key Laboratory of Animal Embryo Engineering and Molecular Breeding, Hubei Academy of Agricultural Sciences, Wuhan 430064, China.
⁵ Key Laboratory of Prevention and Control Agents for Animal Bacteriosis, Ministry of Agriculture and Rural Affairs, Institute of Animal Husbandry and Veterinary, Hubei Academy of Agricultural Sciences, Wuhan 430064, China.
⁶ College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China.
⁷ National Key Laboratory of Agricultural Microbiology, College of Animal Sciences and Veterinary Medicine, Huazhong Agricultural University, The Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070, China. Electronic address: he628@mail.hzau.edu.cn.
⁸ National Key Laboratory of Agricultural Microbiology, College of Animal Sciences and Veterinary Medicine, Huazhong Agricultural University, The Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070, China; Hubei Hongshan Laboratory, Wuhan 430070, China. Electronic address: wentao@mail.hzau.edu.cn.

PMID: 38663699
DOI: 10.1016/j.ijbiomac.2024.131839

Abstract

Streptococcus suis (S. suis) is a significant zoonotic microorganism that causes a severe illness in both pigs and humans and is characterized by severe meningitis and septicemia. Suilysin (SLY), which is secreted by S. suis, plays a crucial role as a virulence factor in the disease. To date, the interaction between SLY and host cells is not fully understood. In this study, we identified the interacting proteins between SLY and human brain microvascular endothelial cells (HBMECs) using the TurboID-mediated proximity labeling method. 251 unique proteins were identified in TurboID-SLY treated group, of which six plasma membrane proteins including ARF6, GRK6, EPB41L5, DSC1, TJP2, and PNN were identified. We found that the proteins capable of interacting with SLY are ARF6 and PNN. Subsequent investigations revealed that ARF6 substantially increased the invasive ability of S. suis in HBMECs. Furthermore, ARF6 promoted SLY-induced the activation of p38 MAPK signaling pathway in HBMECs. Moreover, ARF6 promoted the apoptosis in HBMECs through the activation of p38 MAPK signaling pathway induced by SLY. Finally, we confirmed that ARF6 could increase the virulence of SLY in C57BL/6 mice. These findings offer valuable insights that contribute to a deeper understanding of the pathogenic mechanism of SLY.

Keywords: ARF6; Apoptosis; Streptococcus suis; Suilysin; TurboID-mediated proximity labeling; p38 MAPK signaling pathway.