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Effective decolonization strategy for mupirocin-resistant Staphylococcus aureus by TPGS-modified mupirocin-silver
Ming-Chen Sun1,2, Ying-Fang Chen3, Di Liu2
1Center for Plastic & Reconstructive Surgery, Department of Dermatology, Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College), Hangzhou, 310014, China.
Abstract:
The widespread utilization of mupirocin to treat methicillin-resistant Staphylococcus aureus (MRSA)-caused infectious diseases has led to the emergence of mupirocin-resistant Staphylococcus aureus (MuRSA), posing a serious global medical threat. In order to counteract MuRSA, we develop a d-α-tocopherol polyethylene glycol 1000 succinate (TPGS) modified mupirocin and silver complex (TPGS/Mup-Ag) to combat MuRSA. The surfactivity of TPGS endows Mup-Ag with a homogeneous and small particle size (∼16 nm), which significantly enhances bacterial internalization. Silver ions are released from the mupirocin-Ag complex (Mup-Ag) to exert a synergistic antibacterial activity with mupirocin. Results manifest that our strategy reduces the concentration of mupirocin that induces 50% bacterial death from about 1000 μmol/mL to about 16 μmol/mL. In vitro bacterial infection model suggests that TPGS/Mup-Ag can not only eliminate both intracellular and inhibit bacterial adhesion, but also living cells are not affected. Results of in vivo experiments demonstrate that TPGS/Mup-Ag can effectively inhibit the progression of skin infection and accelerate wound healing, as well as alleviate systemic inflammation in both the subcutaneous infection model and the wound infection model. Furthermore, this study may contribute to the development of therapeutic agents for antibiotic-resistant bacteria and offer ideas for silver-based bactericides.
Insights
A novel d-α-tocopherol polyethylene glycol 1000 succinate (TPGS) modified mupirocin and silver complex (TPGS/Mup-Ag) effectively combats mupirocin-resistant Staphylococcus aureus (MuRSA). This innovative approach significantly reduces required mupirocin concentration and promotes wound healing.
Area of Science:
- Nanotechnology in Medicine
- Antimicrobial Resistance Research
- Drug Delivery Systems
Background:
- Methicillin-resistant Staphylococcus aureus (MRSA) infections are a global health concern.
- Emergence of mupirocin-resistant Staphylococcus aureus (MuRSA) necessitates novel therapeutic strategies.
- Existing treatments face challenges due to increasing antibiotic resistance.
Purpose of the Study:
- To develop a TPGS-modified mupirocin and silver complex (TPGS/Mup-Ag) to combat MuRSA.
- To evaluate the efficacy of TPGS/Mup-Ag against antibiotic-resistant bacteria.
- To explore the potential of silver-based bactericides for resistant infections.
Main Methods:
- Synthesis of d-α-tocopherol polyethylene glycol 1000 succinate (TPGS) modified mupirocin and silver complex (TPGS/Mup-Ag).
- Characterization of particle size and antibacterial activity of TPGS/Mup-Ag.
- In vitro and in vivo models to assess efficacy in bacterial infection and wound healing.
Main Results:
- TPGS modification resulted in small particle size (∼16 nm), enhancing bacterial internalization.
- TPGS/Mup-Ag demonstrated synergistic antibacterial activity, reducing effective mupirocin concentration by approximately 60-fold.
- In vivo studies showed effective inhibition of skin infection, accelerated wound healing, and reduced systemic inflammation.
Conclusions:
- TPGS/Mup-Ag is a promising therapeutic agent against mupirocin-resistant Staphylococcus aureus.
- The developed complex effectively eliminates intracellular bacteria and inhibits adhesion without affecting host cells.
- This study provides a foundation for developing advanced therapeutic agents for antibiotic-resistant bacteria.
