Cell-Penetrating Antimicrobial Peptides Derived from an Atypical Staphylococcal δ-Toxin.

Revisiting underutilized classes of antibiotics is a pragmatic approach to the identification of alternative therapies for antimicrobial-resistant pathogens. To this end, we designed and screened a set of seven staphylococcal δ-toxin-inspired peptides (STIPs) for antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA). Furthermore, a pathogen-specific protease was leveraged to generate shorter peptides from these δ-toxin derivatives to expand the screen of putative antimicrobial peptides (AMPs) and to counterscreen against AMP inactivation.