Anaplasma phagocytophilum AptA enhances the UPS, autophagy, and anti-apoptosis of host cells by PSMG3

Zhongchen Ma; Ruirui Li; Ruirui Hu; Wei Zheng; Shuifa Yu; Kejian Cheng; Huan Zhang; Yangyang Xiao; Jihai Yi; Zhen Wang; Yong Wang; Chuangfu Chen

doi:10.1016/j.ijbiomac.2021.06.039

Anaplasma phagocytophilum AptA enhances the UPS, autophagy, and anti-apoptosis of host cells by PSMG3

Int J Biol Macromol. 2021 Aug 1:184:497-508. doi: 10.1016/j.ijbiomac.2021.06.039. Epub 2021 Jun 11.

Authors

Zhongchen Ma¹, Ruirui Li¹, Ruirui Hu², Wei Zheng¹, Shuifa Yu¹, Kejian Cheng¹, Huan Zhang¹, Yangyang Xiao¹, Jihai Yi¹, Zhen Wang¹, Yong Wang³, Chuangfu Chen⁴

Affiliations

¹ International Research Center for Animal Health Breeding, College of Animal Science and Technology, Shihezi University, 832003 Shihezi, Xinjiang, China; Collaborative Innovation Center for prevention and control of high incidence zoonotic infectious diseases in Western China, College of Animal Science and Technology, Shihezi University, 832003 Shihezi, Xinjiang, China.
² College of Life Sciences, Shihezi University, 832003 Shihezi, Xinjiang, China.
³ International Research Center for Animal Health Breeding, College of Animal Science and Technology, Shihezi University, 832003 Shihezi, Xinjiang, China; Collaborative Innovation Center for prevention and control of high incidence zoonotic infectious diseases in Western China, College of Animal Science and Technology, Shihezi University, 832003 Shihezi, Xinjiang, China. Electronic address: yongwang@shzu.edu.cn.
⁴ International Research Center for Animal Health Breeding, College of Animal Science and Technology, Shihezi University, 832003 Shihezi, Xinjiang, China; Collaborative Innovation Center for prevention and control of high incidence zoonotic infectious diseases in Western China, College of Animal Science and Technology, Shihezi University, 832003 Shihezi, Xinjiang, China. Electronic address: chuangfu_chen@163.com.

PMID: 34126152
DOI: 10.1016/j.ijbiomac.2021.06.039

Abstract

Anaplasma phagocytophilum is an obligate intracellular bacterium and a common tick-borne infectious pathogen that can cause human granulocytic anaplasmosis (HGA). Effector proteins play an important role in the pathogenic mechanism of A. phagocytophilum, but the specifics of the disease mechanism are unclear. We studied the effector protein AptA (A. phagocytophilum toxin A) using yeast two hybrid assays to screen its interacting protein proteasome assembly chaperone 3 (PSMG3, PAC3), and identified new mechanisms for the pathogenicity of A. phagocytophilum in HEK293T cells. After AptA enters the host cell, it interacts with PSMG3 to enhance the activity of the proteasome, causing ubiquitination and autophagy in the host cell and thereby increasing cross-talk between the ubiquitination-proteasome system (UPS) and autophagy. AptA also reduces the apoptotic efficiency of the host cells. These results offer new clues as to the pathogenic mechanism of A. phagocytophilum and support the hypothesis that AptA interacts with host PSMG3.

Keywords: Anaplasma phagocytophilum AptA; Apoptosis; Autophagy; PSMG3; Ubiquitin-proteasome system (UPS).

MeSH terms

Anaplasma phagocytophilum / metabolism
Anaplasma phagocytophilum / pathogenicity*
Autophagy
Bacterial Toxins / metabolism*
HEK293 Cells
Host-Pathogen Interactions
Humans
Molecular Chaperones / metabolism*
Proteasome Endopeptidase Complex / metabolism
Two-Hybrid System Techniques
Ubiquitination

Substances

Bacterial Toxins
Molecular Chaperones
PSMG3 protein, human
Proteasome Endopeptidase Complex