Functional targeting of bacteria: A multimodal construct for PDT and diagnostics of drug-resistant bacteria

Abstract

A multimodal construct that targets functionality unique to pathogens, but typically absent in mammals, is the focus of this chapter. A brief overview of antimicrobial photodynamic therapy (PDT) and targeting strategies is provided for context only, followed by the development of the functional targeting that is the substance of this chapter. Deeper reviews on PDT and antimicrobial PDT are topics of other chapters in this book, and other publications. The constructs termed β-lactamase enzyme-activated photosensitizer (β-LEAP)/β-lactamase enzyme-activated fluorophore (β-LEAF) and their potential applications and significance are described in the context of existing technologies. The conclusions with the current state of the art is that this methodology may provide a practical and rapid test for establishing the utility of antibiotics to specific infections, thus reducing the empirical use of these drugs and lowering the incidence of development of drug-resistant pathogens. A less developed aspect of the chapter is the potential for the use of these same constructs in PDT, where they can be used to eradicate lactamase-based drug-resistant bacteria that survive conventional antibiotic treatments, in addition to drug-sensitive bacteria. The chapter ends with a perspective on the broader potential of this platform in microbiology and parasitology.