2. Academic Validation
  3. Use of mouse primary epidermal organoids for USA300 infection modeling and drug screening

Use of mouse primary epidermal organoids for USA300 infection modeling and drug screening

  • Cell Death Dis. 2023 Jan 11;14(1):15. doi: 10.1038/s41419-022-05525-x.
Xiaorui Xie # 1 2,  Xuebo Tong # 3,  Zhihong Li 2,  Quan Cheng 2,  Xiaowei Wang 2,  Yin Long 4,  Fangbo Liu 2,  Yonghui Wang 5,  Juan Wang 6,  Li Liu 7
Affiliations

Affiliations

  • 1 School of Pharmacy, Fudan University, Shanghai, China.
  • 2 Shanghai Drugability Biomass Product Evaluation Professional Public Service Platform, Center for Pharmacological Evaluation and Research, China State Institute of Pharmaceutical Industry, Shanghai, China.
  • 3 Shanghai Children's Medical Center affiliated to the Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 4 Department of Traditional Chinese Medicine, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, 710032, China.
  • 5 School of Pharmacy, Fudan University, Shanghai, China. [email protected].
  • 6 Shanghai Drugability Biomass Product Evaluation Professional Public Service Platform, Center for Pharmacological Evaluation and Research, China State Institute of Pharmaceutical Industry, Shanghai, China. [email protected].
  • 7 Shanghai Drugability Biomass Product Evaluation Professional Public Service Platform, Center for Pharmacological Evaluation and Research, China State Institute of Pharmaceutical Industry, Shanghai, China. [email protected].
  • # Contributed equally.
PMID: 36631452 DOI: 10.1038/s41419-022-05525-x
Abstract

Skin infections caused by drug-resistant Staphylococcus aureus occur at high rates nationwide. Mouse primary epidermal organoids (mPEOs) possess stratified histological and morphological characteristics of epidermis and are highly similar to their derived tissue at the transcriptomic and proteomic levels. Herein, the susceptibility of mPEOs to methicillin-resistant S. aureus USA300 Infection was investigated. The results show that mPEOs support USA300 colonization and invasion, exhibiting swollen epithelial squamous cells with nuclear necrosis and secreting inflammatory factors such as IL-1β. Meanwhile mPEOs beneficial to observe the process of USA300 colonization with increasing Infection time, and USA300 induces mPEOs to undergo Pyroptosis and Autophagy. In addition, we performed a drug screen for the mPEO Infection model and showed that vancomycin restores cell viability and inhibits Bacterial internalization in a concentration-dependent manner. In conclusion, we establish an in vitro skin Infection model that contributes to the examination of drug screening strategies and antimicrobial drug mechanisms.

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