Antibacterial activity of light triggered antibiotics against uropathogenic bacteria

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The exponential growth of microbial multidrug resistance in nosocominal infections has been extensively reported in medical practice and has currently emerged as a serious threat to public health. Infections of the urinary tract are significant not only due to their high incidence, but also for being the most common reason to prescribe antibiotics, which contributes to the development of resistances. Antimicrobial photodynamic therapy represents a highly promising alternative treatment against localized microbial infections caused by antibiotic resistant bacteria. It employs a non-toxic dye termed a photosensitizer (PS) and low-intensity visible light, which in the presence of molecular oxygen is able to produce cytotoxic species. Yet, in order to transfer this promising diagnostic and therapeutic method to regular clinical practice, additional well-designed studies are needed, including the development of targeted photosensitizers. Herein, a promising general approach is proposed to enable the selective and specific binding of PS to lipopolysaccharides as particularly attractive targets for the development of new antibacterial agents. Besides providing a protective barrier, lipopolysaccharides are of great interest due to their potent inflammatory effects and their contribution to biofilm formation. The final aim of this project is to investigate the interplay between structural features of tailored phthalocyanine conjugates, their photophysical properties and their killing efficiency against uropathogenic E. coli strains including multiresistant isolates in planktonic and biofilm cultures. The enhanced affinity of the PS for bacterial cells will enable a selective delivery of PS to the infection site leading to inactivation with minimal non-specific drug accumulation.