Porphycene-apidaecin conjugate: a new broad spectrum antimicrobial agent

Photodynamic therapy (PDT) and the use of cationic antimicrobial peptides (AMPs) are two very promising strategies to combat antibiotic resistant bacteria. Recently, we demonstrated that the conjugation of a porphyrin photosensitizer with Apidaecin 1b, a small peptide belonging to the Pro- Arg rich AMPs family, provides a potent antimicrobial agent with broad spectrum activity. Porphycenes are structural isomers of porphyrins with 10-fold higher absorption coefficient in the red part of the spectrum, and excellent photochemical and photodynamic properties .Therefore, in an attempt to improve the potential application of the photosensitizer-peptide conjugates, we extended our studies to a porphycene-apidaecin conjugate, in which the porhycene is linked to the N-terminus of Apidaecin. The antibacterial activity of the conjugate (hereafter G-api) has been tested against Gram negative (E. coli) and Gram positive (methicillin resistant S. aureus) bacteria. The phototoxic activity against eukaryotic cells will also be measured to evaluate selectivity. In the dark G-api did not exhibit any toxicity against both E. coli and S. aureus. On the contrary, following activation with red light (36 J/cm2), G-api caused a significant (3-4 log10) reduction of both E. coli and S. aureus survival. Under the same experimental condition porphycene plus Apidaecin, administrated together but not conjugated, did not affect the survival of both E. coli and S. aureus. The G-api conjugate therefore appears a very promising agent for the photoinactivation of both Gram positive and Gram negative bacteria.