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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 …