Protein-A-mediated targeting of Bacteriochlorophyll-IgG to Staphylococcus aureus:: A model for enhanced site-specific photocytotoxicity

A model for studying the efficiency of photodynamic action with a photosensitizer placed exclusively on the bacterial cell mall has been used, Bacteriochlorophyllide molecules, conjugated to rabbit immunoglobulin G (IgG), were synthesized. The conjugated pigment bacteriochlorophyll (Bchl)-IgG bound with high specificity to protein-A residues naturally exposed on the cell wall of the bacterium Staphylococcus aureus Cowan I, In bacterial suspensions the phototoxicity of the targeted conjugates (0.5-2.5 pigment per IgG molecule) was dose dependent (LD50 = 1.7 mu M in the presence of Light (lambda > 550 nm) and inhibited by native IgG but not by ovalbumin, suggesting selective interaction with protein-A on the bacterial cell wall, No dark toxicity was noticed even with the highest conjugate concentration tested, In contrast, the photocytotoxicity of bacteriochlorophyll-serine (Bchl-Ser, LD50 = 0.07 mu M) used as a nontargeted control was not inhibited by IBG. In spite of its lower apparent potency, Bchl-IgG was found to be 30 times more efficacious than Bchl-Ser: At LD50, only 66 000 Bchl-IgG molecules were bound per bacterium compared to 1900 000 molecules of Bchl-Ser, The higher efficacy of Bchl-IgG is explained by its exclusive position on the bacterial cell wall, Consequently, photogeneration of oxidative species is confined to the cell wall and its vicinity, a seemingly highly susceptible domain for photodynamic action, In considering the design of cell-specific sensitizers for bacterial and cancer therapies, it would be beneficial to identify the more discretely sensitive subcellular domains as targets.