1. Academic Validation
  2. Staphylococcus aureus extracellular vesicles induce apoptosis and restrain mitophagy-mediated degradation of damaged mitochondria

Staphylococcus aureus extracellular vesicles induce apoptosis and restrain mitophagy-mediated degradation of damaged mitochondria

  • Microbiol Res. 2023 May 30;273:127421. doi: 10.1016/j.micres.2023.127421.
Xiaozhou Wang 1 Hongyan Li 2 Jie Wang 3 Huiling Xu 4 Kun Xue 1 Xiaoting Liu 1 Zhizhong Zhang 1 Jianzhu Liu 5 Yongxia Liu 6
Affiliations

Affiliations

  • 1 College of Veterinary Medicine, Shandong Agricultural University, Tai`an 271018, China.
  • 2 The Affiliated Taian City Central Hospital of Qingdao University, Tai`an 271000, China.
  • 3 Xinjiang Key Laboratory of Animal Infectious Diseases, Institute of Veterinary Medicine, Xinjiang Academy of Animal Science, Urumqi 830013, China.
  • 4 Research Center for Animal Disease Control Engineering, Shandong Agricultural University, Tai`an 271018, China.
  • 5 College of Veterinary Medicine, Shandong Agricultural University, Tai`an 271018, China; Research Center for Animal Disease Control Engineering, Shandong Agricultural University, Tai`an 271018, China. Electronic address: [email protected].
  • 6 College of Veterinary Medicine, Shandong Agricultural University, Tai`an 271018, China. Electronic address: [email protected].
Abstract

Extracellular vesicles (EVs) are nano-sized bilayer EVs with various components. EV secretion in pathogenic Gram-positive bacteria is a universal feature that can cause disease and damage the targeted host. In this study, we isolated and purified Staphylococcus aureus (S. aureus) EVs, and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analyzed Ev's protein composition. After that, the pathway of EVs internalized into MAC-T cells was evaluated. Moreover, the activation of mitogen-activated protein kinase (MAPK) and the nuclear factor κB (NF-κB) pathway was measured by Western blot. Meanwhile, Western blot and confocal microscopy detected mitochondrial damage, Apoptosis, and Parkin-mediated Mitophagy. Results showed that purified S. aureus EVs exhibited a typical cup-shaped structure and internalized into MAC-T cells by lipid raft-mediated endocytic pathway. S. aureus EVs caused mitochondrial damage and Apoptosis in MAC-T cells. However, degradation of the damaged mitochondria was impeded due to the Parkin-mediated Mitophagy pathway being restrained by the disruption of the acidic environment of lysosomes by S. aureus EVs. Hence, our study reveals the role of S. aureus EVs in immune stimulation, disruption of mitochondria, and lysosomal acidic environment in bovine mammary epithelial cells. These findings help us understand the role of EVs in the pathogenic mechanism of S. aureus.

Keywords

Apoptosis; Extracellular vesicles; Mitochondria; Mitophagy; Staphylococcus aureus.

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