Conjugation of Antimicrobial Peptide to Zinc Phthalocyanine for an Efficient Photodynamic Antimicrobial Chemotherapy

Abstract

Photodynamic antimicrobial chemotherapy is an attractive and novel therapeutic approach to treat microbial infections. Antimicrobial peptides (AMPs) have the potential to specifically target and kill the microorganism while showing no effect toward mammalian cells. In the current study, antimicrobial peptide (GGG(RW)3), an analogue of MP-196, was conjugated to a zinc phthalocyanine (ZnPc) photosensitizer (PS) for photoinactivation assay to enhance the bacterial killing efficacy of the peptide. The AMPs showed selectivity toward the Gram-positive strain of bacteria. We observed that the conjugate ZnPc-GGG(RW)3 also displayed a photoinactivation effect against the Gram-positive strains of S. aureus. The results showed that ZnPc-GGG(RW)3 induced a 6-log reduction (i.e., 99.999% cell killing) in Gram-positive S. aureus at a light dose of 22 J/cm2 upon illumination under red light, while the peptide did not exhibit such a significant effect when tested alone at the same concentration. The conjugate also showed 50% inhibition of the bacterial strain in the dark at a higher concentration. Furthermore, the addition of potassium iodide salt to the PS at lower concentrations also significantly killed the Gram-negative E. coli strain and killed the E. coli strain with up to a 5-log reduction at a light dose of 22 J/cm2 under red light illumination. We demonstrated the efficacy of antimicrobial peptide (GGG(RW)3 enhanced by conjugation to a ZnPc photosensitizer.