Cationic antimicrobial peptide LL-37 is effective against both extra-and intracellular Staphylococcus aureus. Antimicrob Agents Chemotherap 2013;57:1283

The increasing resistance of bacteria to conventional antibiotics and the challenges posed by intracellular bacteria, which may be responsible for chronic and recurrent infections, have driven the need for advanced antimicrobial drugs for effective elimination of both extra- and intracellular pathogens. The purpose of this study was to determine the killing efficacy of cationic antimicro-bial peptide LL-37 compared to conventional antibiotics against extra- and intracellular Staphylococcus aureus. Bacterial killing assays and an infection model of osteoblasts and S. aureuswere studied to determine the bacterial killing efficacy of LL-37 and conventional antibiotics against extra- and intracellular S. aureus. We found that LL-37 was effective in killing extracellular S. aureus at nanomolar concentrations, while lactoferricin B was effective at micromolar concentrations and doxycycline and cefa-zolin at millimolar concentrations. LL-37 was surprisingly more effective in killing the clinical strain than in killing an ATCC strain of S. aureus. Moreover, LL-37 was superior to conventional antibiotics in eliminating intracellular S. aureus. The kinetic studies further revealed that LL-37 was fast in eliminating both extra- and intracellular S. aureus. Therefore, LL-37 was shown to be very potent and prompt in eliminating both extra- and intracellular S. aureus and was more effective in killing extra- and in-tracellular S. aureus than commonly used conventional antibiotics. LL-37 could potentially be used to treat chronic and recur-rent infections due to its effectiveness in eliminating not only extracellular but also intracellular pathogens. Conventional antibiotics are becoming increasingly ineffectivedue to rapidly evolving multidrug-resistant bacterial strains. The heavy use of antibiotics is causing bacteria to mutate an