Bacteria-specific pro-photosensitizers: An emerging field in phototherapy for multidrug-resistant bacteria (Keynote Presentation)

In the past two decades, many photosensitizers (PS) have been developed for photodynamic therapy (PDT) targeting cancers, microbial pathogens, and parasites in both clinical and pre-clinical settings. However, none of these PS are specific for bacteria. Given the growing threat of multidrug-resistant (MDR) bacteria, non-antibiotic approaches are actively sought after to battle these resilient microbes. To date, we will discuss bacteria-specific pro-PS that are activated exclusively in bacteria, but not in mammalian cells, distinguishing them from traditional PS that are active in both mammalian cells and bacteria. Two classes of pro-PS will be discussed: those that convert to PS from non-PS specifically in bacteria owing to higher levels of singlet oxygen production in bacteria upon light illumination and those utilizing porphyrin precursors in a bacteria-specific pathway to increase porphyrin biosynthesis. Because of the specificity, these pro-PS can be employed at high concentrations in conjunction and effectively eradicate a range of MDR bacteria, including their planktonic forms, mature biofilms, and persisters, irrespective of their antibiotic susceptibility.