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Published on: September 8, 2021
Evaluation of LL-37 antimicrobial peptide derivatives alone and in combination with vancomycin against S. aureus
James F Shurko1,2, Ralph S Galega1, Chuxi Li1
1College of Pharmacy, The University of Texas at Austin, Austin, TX, 78712, USA.
Abstract:
Treatment of Staphylococcus aureus infections continues to be a challenge due to antimicrobial resistance. Endogenous antimicrobial peptides may offer a new option for treating S. aureus infections but several factors limit their clinical utility. Herein, we studied the activity of the antimicrobial peptide LL-37 and two truncated derivatives, LL-13 and LL-17 alone and in combination with vancomycin against a range of drug-resistant S. aureus strains including methicillin resistant S. aureus (MRSA) and vancomycin resistant S. aureus (VRSA) strains in vitro. When used with vancomycin, LL-13 and LL-17 displayed synergy against VRSA and showed the ability to restore sensitivity to vancomycin after pretreatment. In addition, LL-13 and LL-17 showed a strong ability to inhibit S. aureus biofilm production. LL-37 derivatives may be useful in treating infections that are resistant to vancomycin or in scenarios where biofilm formation is a concern.
Insights
Antimicrobial peptides LL-13 and LL-17 show promise in combating drug-resistant Staphylococcus aureus infections. These peptides, when combined with vancomycin, restore sensitivity and inhibit biofilm formation in vitro.
Area of Science:
- Microbiology
- Infectious Diseases
- Biochemistry
Background:
- Antimicrobial resistance in Staphylococcus aureus, including MRSA and VRSA, poses a significant clinical challenge.
- Endogenous antimicrobial peptides (AMPs) represent a potential therapeutic avenue, but their clinical application is often limited.
- The antimicrobial peptide LL-37 and its derivatives are being investigated for their activity against resistant bacterial strains.
Purpose of the Study:
- To evaluate the in vitro activity of the antimicrobial peptide LL-37 and its truncated derivatives, LL-13 and LL-17.
- To assess the synergistic effects of LL-13 and LL-17 in combination with vancomycin against drug-resistant Staphylococcus aureus strains.
- To determine the efficacy of LL-13 and LL-17 in inhibiting Staphylococcus aureus biofilm formation.
Main Methods:
- In vitro susceptibility testing of Staphylococcus aureus strains (including MRSA and VRSA) against LL-37, LL-13, LL-17, and vancomycin.
- Checkerboard assays to evaluate synergistic activity between peptides and vancomycin.
- Biofilm inhibition assays to assess the anti-biofilm properties of the peptides.
Main Results:
- LL-13 and LL-17 demonstrated synergistic activity with vancomycin against vancomycin-resistant S. aureus (VRSA).
- Pretreatment with LL-13 and LL-17 restored vancomycin sensitivity in VRSA strains.
- Both LL-13 and LL-17 exhibited potent inhibition of Staphylococcus aureus biofilm production in vitro.
Conclusions:
- LL-37 derivatives, specifically LL-13 and LL-17, show potential as adjunct therapies for vancomycin-resistant Staphylococcus aureus infections.
- These peptides may be valuable in treating infections where biofilm formation is a contributing factor.
- Further research into LL-37 derivatives could lead to novel strategies against challenging S. aureus infections.
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