Use of mouse primary epidermal organoids for USA300 infection modeling and drug screening
Xiaorui Xie1,2, Xuebo Tong3, Zhihong Li2
1School of Pharmacy, Fudan University, Shanghai, China.
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.
Insights
This study establishes a novel mouse organoid model for studying drug-resistant Staphylococcus aureus skin infections. The model effectively simulates infection, allowing for drug screening and mechanism investigation.
Area of Science:
- Microbiology and Infectious Diseases
- Dermatology
- Drug Discovery
Background:
- Drug-resistant Staphylococcus aureus, particularly methicillin-resistant S. aureus (MRSA) USA300, causes significant skin infections.
- Mouse primary epidermal organoids (mPEOs) mimic human epidermis structure and gene expression.
- A reliable in vitro model is needed to study MRSA skin infections and test antimicrobial agents.
Purpose of the Study:
- To investigate the susceptibility of mPEOs to MRSA USA300 infection.
- To characterize the host-pathogen interactions and cellular responses within the mPEO model.
- To establish and validate mPEOs as a platform for antimicrobial drug screening.
Main Methods:
- Infection of mPEOs with MRSA USA300.
- Histological and molecular analysis of infected organoids.
- Assessment of inflammatory factor secretion (e.g., IL-1β).
- Observation of bacterial colonization and invasion over time.
- Drug screening using vancomycin.
Main Results:
- mPEOs support MRSA USA300 colonization and invasion.
- Infected mPEOs show swollen cells, nuclear necrosis, and secretion of IL-1β.
- MRSA USA300 induces pyroptosis and autophagy in mPEOs.
- Vancomycin demonstrated concentration-dependent restoration of cell viability and inhibition of bacterial internalization.
Conclusions:
- mPEOs provide a robust in vitro model for studying MRSA skin infections.
- This model facilitates the observation of infection dynamics and host responses.
- The mPEO infection model is suitable for evaluating antimicrobial drug efficacy and mechanisms.
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