Impact of IMT-P8 on the Efficacy of Conventional Antibiotics for the Treatment of Drug-Resistant and Intracellular <i>Staphylococcus aureus</i>

Addressing the issue of antimicrobial resistance is of the utmost importance on a global scale. We are in dire need of innovative methods and alternatives to new antibiotic discovery in order to address the growing problem of antimicrobial resistance. In this study, we investigated the efficacy of cell-penetrating peptide (IMT-P8) as an adjuvant to enhance the activity of conventional antibiotics against multidrug-resistant and intracellular <i>Staphylococcus aureus</i> in vitro and in vivo<i>.</i> IMT-P8 potentiates various antibiotics belonging to different classes. The best combination was found with clarithromycin; IMT-P8 modulated its activity by 256-fold. The IMT-P8 + clarithromycin combination showed excellent antibiofilm and intracellular pathogen-killing activity against MRSA GMCH 839. The remarkable effectiveness of IMT-P8 was demonstrated in murine superficial skin infection and sepsis survival models. The safety studies show that IMT-P8 exhibits no toxicity at its effective concentration in vitro and in vivo. These findings suggest that IMT-P8 could be a promising antibiotic adjuvant for treating severe bacterial infections caused by MRSA.