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The protective effect of Schisandrin C against methicillin-resistant Staphylococcus aureus-induced otitis media
Weifang Sun1, Meihui Tian2, Xingye Wang1
1Traditional Chinese Medicine College, Changchun University of Chinese Medicine, Changchun, Jilin, China.
Abstract:
Methicillin-resistant Staphylococcus aureus (MRSA) is a significant pathogen in otitis media (OM), including acute otitis media (AOM) and chronic suppurative otitis media (CSOM), presenting considerable therapeutic challenges due to its biofilm formation, host immune evasion, and promotion of persistent inflammation. This study evaluated the therapeutic potential of Schisandrin C (Sch C), a natural lignan derived from Schisandra chinensis, in mitigating MRSA-induced OM. In rat models of MRSA-induced AOM and CSOM, Sch C significantly reduced bacterial load and inflammatory responses by decreasing pro-inflammatory cytokine levels. By upregulating tight junction protein ZO-1 and downregulating mucin MUC5B, it also restored epithelial barrier integrity. In addition, Sch C treatment improved auditory function. Mechanistic studies revealed that Sch C directly inhibited sortase A (SrtA), a key enzyme responsible for anchoring surface virulence factors in MRSA, by binding to its active site and inhibiting its transpeptidase activity (fluorescence resonance energy transfer IC₅₀ = 38.68 µM). Through inhibiting SrtA, Sch C disrupted MRSA adhesion, invasion, and biofilm formation without exerting direct bactericidal effects. Furthermore, Sch C synergized with ofloxacin, enhancing its efficacy against MRSA otitis by reducing bacterial load, inflammation, and tissue damage. Collectively, these findings establish Sch C as a potent S. aureus SrtA inhibitor, highlighting its promise as a therapeutic strategy for MRSA-induced OM.
Insights
Schisandrin C effectively treats methicillin-resistant Staphylococcus aureus (MRSA) otitis media by inhibiting sortase A, reducing inflammation, and restoring the epithelial barrier. It also enhances antibiotic efficacy, offering a promising therapeutic approach.
Area of Science:
- Microbiology
- Pharmacology
- Otolaryngology
Background:
- Methicillin-resistant Staphylococcus aureus (MRSA) poses significant challenges in treating otitis media (OM) due to its virulence factors and resistance.
- Current therapies for MRSA-induced OM are limited, necessitating novel treatment strategies.
Purpose of the Study:
- To evaluate the therapeutic potential of Schisandrin C (Sch C) in a rat model of MRSA-induced otitis media (OM).
- To investigate the mechanism of action of Sch C, focusing on its inhibitory effects on MRSA virulence factors.
Main Methods:
- MRSA-induced acute otitis media (AOM) and chronic suppurative otitis media (CSOM) were established in rat models.
- Sch C treatment was administered, and its effects on bacterial load, inflammatory markers, epithelial barrier integrity, and auditory function were assessed.
- Mechanistic studies involved evaluating Sch C's inhibitory activity against sortase A (SrtA) using fluorescence resonance energy transfer (FRET).
- Synergistic effects of Sch C with ofloxacin were investigated.
Main Results:
- Sch C significantly reduced bacterial load and pro-inflammatory cytokine levels in MRSA-induced OM.
- Treatment with Sch C restored epithelial barrier integrity by modulating tight junction protein ZO-1 and mucin MUC5B.
- Sch C directly inhibited MRSA sortase A (SrtA) activity, disrupting bacterial adhesion, invasion, and biofilm formation.
- Sch C demonstrated synergistic effects with ofloxacin, enhancing its therapeutic efficacy against MRSA otitis.
Conclusions:
- Schisandrin C is a potent inhibitor of MRSA sortase A, offering a novel therapeutic strategy for MRSA-induced otitis media.
- Sch C mitigates inflammation, restores epithelial barrier function, and improves auditory outcomes in OM.
- The combination of Sch C with existing antibiotics like ofloxacin may enhance treatment effectiveness for resistant bacterial infections.
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