Uncovering evolutionary trajectories and genetic divergence shaped by single antimicrobial peptides and their combinations

The emergence of antimicrobial resistance (AMR) in bacteria poses a significant threat to global health. Staphylococcus aureus is a prominent example, as its resistance to conventional antibiotics is reaching alarming rates. Antimicrobial peptides (AMPs) offer a promising alternative therapeutic approach to fight antibiotic resistance pathogens. However, few studies have shown resistance development towards AMPs. Nevertheless, the mechanisms underlying resistance to single AMPs, and particularly their combinations, remain poorly understood. Here, we investigated the genetic mechanisms of resistance evolution in S. aureus exposed to individual AMPs (Temporin, Melittin and Pexiganan) and their combinations. We compared the genetic profiles of evolved strains to identify similarities and differences in resistance pathways between individual and combination treatments.