Exploring the efficacy of novel photobactericidals against planktonic and biofilm growing uropathogenic bacteria

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Worldwide thousands of patients suffer from urinary tract infection (UTI). Current treatments of UTI are commonly based on high concentration of systemically applied antibiotics. A disadvantage in this treatment lies in the promoted development of (multi)resistances. Antimicrobial photodynamic therapy is alternative, non-antibiotic based treatment method that allows us to meet current challenges in a very effective way; it does not lead to the selection of resistant mutants and can destroy pathogens in a short time frame by the combined action of a photosensitizer and near infrared light. The selective and specific binding of photosensitizer to lipopolysaccharides as particularly attractive targets is envisaged, complementing our previous work on the search for PSs that might be considered good candidates for the photoinactivation of Gram-negative bacteria. We aim to modulate the chemical structure of photosensitizers so that they can be rapidly taken up by Gram-negative bacteria at low concentrations and kill microorganisms but not damage the host tissue. The proteomic analysis will be used to increase our insight into the sequential steps by which microorganisms are photoinactivated. The resistance of bacterial biofilms against antibiotic treatment is one of the major reasons why those who get UTI are highly susceptible to getting more in the future. In this project, we aim to disperse formed biofilms upon photodynamic action. In addition, we will use the photosensitizers for the development of innovative, self-regulated coatings to prevent and treat catheter-associated urinary tract infections. Photocytotoxic characteristics of photosensitizers and model surfaces against a range of clinically important Gram-negative bacteria will be determined.