Antimicrobial and antiviral activity of porphyrin photosensitization

The development of photodynamic therapy (PDT) has provided an effective modality against antibiotic-resistant bacteria and cell free viruses. The antibacterial activity of porphyrin induced photodynamic therapy shows unique properties: I. it is independent of the antibiotic sensitivity spectrum of the treated pathogen and II it has an efficient and non-recovering anti-microbial killing effect upon illumination of Gram positive bacteria. Bacterial PDT is affected by the use of various sensitizers, as a general rule non-charged or positively charged molecules are effective in photoinactivation of Staphylococcus aureus. In order to photosensitize Gram (-) bacteria such as Pseudomonas aeuruginosa and Escherichia coli, we introduced the small peptide polymyxin-B nona-peptide (PBNP) which stimulated the translocation of porphyrin through the outer membrane of these bacteria and makes PDT possible. Gram negative cell killing by the use of PBNP and DP broadens the antibacterial spectrum of photodynamic inactivation and opens new horizons for this modality as a wide spectrum drug when antibiotic resistance is the main concern. Plasmidial and chromosomal DNA damage in S. aureus and E. coli cells was mediated by DP photosensitization. The major observation was the disappearance of the plasmid supercoiled fraction. The chromosomal DNA was also affected and its degradation products were detected after treatment. Porphyrin-mediated photosensitization is effective against free viruses, virus-transformed cells and the viral contaminants in blood. Specific photodynamic inactivation of free Friend leukemia viruses and cell-associated virions of the virus complex was attained by HPD. Our most recent results depict the PDT sensitive phases of Herpes simplex (HSV-1, HSV-2) Varicella zoster and the nonenveloped Adeno- 2 viruses. These viruses were treated with different derivatives of phthalocyanines modified both by their side chains and their metal substitutes during short time intervals of their adsorption to the target cells. Specific phthalocyanines were highly effective in photoinactivation of the viruses during the initial stage prior to viral-endocytosis and during this process. These new photosensitizers may act as potent viral disinfectant.