Microbial Photodynamic Inactivation (PDI) with meso-Pyridyl Porphyrin Isomers Under Metabolic Gene Knockouts

Microbial Photodynamic Inactivation (PDI) with meso-Pyridyl Porphyrin Isomers Under Metabolic Gene Knockouts

Alvin Sherman Library

Photodynamic Inactivation (PDI) is an antimicrobial technique that functions independently of conventional antibiotic resistance by combining light, photosensitizers, and oxygen in order to eliminate pathogens. Drug-resistant microorganisms have long posed a global challenge, increasing the need for methods that prevent microbes from acquiring further immune adaptations. Photosensitizers serve as compounds that, upon light activation, generate reactive oxygen species (ROS) in order to induce microbial membrane damage and cell death, while also showing effects against cancerous mammalian cells. An investigation was conducted on three meso-Tetra(N-methyl-pyridyl) porphyrin tetrachloride isomers, examining their three conformations of nitrogen substitutions in both freebase and copper-metalated forms. Such porphyrins were chosen due to their chemical reactivity, allowing for interactions with the gram-negative Escherichia coli cell wall. In order to evaluate antimicrobial effectiveness, minimum inhibitory concentration (MIC) assays were conducted in order to establish the lowest concentrations required for efficient microbial elimination. In select assays, genetic removal of key genes involved in the ROS generation of E. coli provided insight into the primary mechanisms governing antimicrobial activity. Fluroescence and UV-Vis spectra were also generated in order to connect electronic properties with singlet oxygen production. The overarching goal of this research is to refine PDI as a viable antimicrobial approach, providing a strategy to combat microorganisms without enabling resistance development.