Siderophore-
photosensitizer conjugates, their synthesis and use in photodynamic
antimicrobial therapy (PACT) is disclosed. The
advantage of this method is improvement of photodynamic
antimicrobial therapy against, for example, pathogenic micro-organisms such as
bacteria and fungi. Naturally occurring and synthetically available
siderophore structures are conjugated chemically with photoactive compounds such as
Chlorin e6 to improve their penetration into bacterial cells and to increase
antibacterial efficacy of photosensitizers via microbial proteins that recognize and transport iron-loaded siderophores. In this way, photosensitizers can be transported inside
bacteria that otherwise could not cross the
cell wall and membranes. Photodynamic activation of photosensitizers inside the cells of pathogenic microbes enables a more effective inhibition of
cellular functions than application at the outer side of the cells. The
siderophore-transporting systems of microbes are known to be specific for
bacteria and fungi. Consequently,
siderophore conjugates with photosensitizers are not taken up by mammalian cells and photodynamic effects can thus be exerted specifically on pathogenic microbes. Applications of these conjugates include highly efficient treatment of pathogenic
gram-negative and -positive bacteria such as
Pseudomonas aeruginosa,
Escherichia coli,
Streptococcus pyogenes,
Staphylococcus aureus, treatment of microbial infections that often occur in chronic wounds as well as therapy of other antibiotic resistant microbial infections.