Bacteriocin AP7121 as a potential treatment for surgical site infections by Staphylococcus aureus: in vitro/in vivo models

Abstract

Surgical site infections (SSIs) are among the leading healthcare-associated infections worldwide, and S. aureus is the most prevalent cause. Antimicrobial resistance, dormant cells, and biofilm formation contribute to treatment failure in SSIs. Therefore, new therapeutic approaches are needed to fight SSIs. The bacteriocin AP7121 has previously shown in vitro bactericidal and anti-biofilm activity against multi-resistant S. aureus. This study aimed to advance on the characterization of the in vitro activity of AP7121 against dormant forms of methicillin- resistant S. aureus (MRSA) and its effect on the adherence of a biofilm-producing strain to sutures. Additionally, a preliminary murine model of SSIs was utilized to proceed toward the in vivo application of AP7121, comparing its antimicrobial potency with the commercial antibiotic Cefazolin. Initially, MRSA cultures were grown to the logarithmic growth phase and subsequently exposed to varying concentrations of AP7121. Viable bacterial counts were assessed at different times of incubation. AP7121 demonstrated a concentration-dependent effect on dormant cells of MRSA when using 8xMIC. The effect of AP7121 on the adherence of biofilm-producing S. aureus to suture surfaces was subsequently evaluated using scanning electron microscopy. AP7121 showed significant inhibitory effects on the adherence of S. aureus in suture threads. Finally, AP7121 demonstrated a significant in vivo bactericidal effect against S. aureus in SSI model. The reduction in viable bacterial counts compared to the control group exceeded 90 % for both Cefazolin and AP7121 treatments. These preliminary f indings highlight AP7121 as a novel and promising antimicrobial peptide for potential applications in human and veterinary medicine.