Development of a Potent Antimicrobial Peptide With Photodynamic Activity

The emergence of antibiotic-resistant bacteria poses a serious challenge to medical practice worldwide. A small peptide with sequence RWRWRW was previously identified as a core antimicrobial peptide with limited antimicrobial spectrum to bacteria, especially Gram-positive bacteria. By conjugating this peptide and its analogs with lipophilic phthalocyanine (Pc), we identified a new antibiotic peptide [PcG(3)K(5)(RW)(3)]. The peptide demonstrates increased antimicrobial effect to both Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli. In addition, Pc also provides added and potent antimicrobial effect upon red light illumination. The inhibitory efficacy of PcG(3)K(5)(RW)(3) was increased by ~140-fold to nanomolar range upon illumination. Moreover, PcG(3)K(5)(RW)(3) was safe for mammalian cell and promoted wound healing in the mouse infection model. Our work provides a new direction to optimize antimicrobial peptides to enhance antimicrobial efficacy.