Riboflavin-Vancomycin Conjugate Enables Simultaneous Antibiotic Photo-Release and Photodynamic Killing against Resistant Gram-Positive Pathogens

Decades of antibiotic misuse have led to alarming levels of antimicrobial resistance, and the development of alternative diagnostic and therapeutic strategies to delineate and treat infections is a global priority. In particular, the nosocomial, multidrug-resistant "ESKAPE" pathogens such as Gram-positive methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus spp (VRE) urgently require alternative treatments. Here, we developed light-activated molecules based on the conjugation of the FDA-approved photosensitizer riboflavin to the Gram-positive specific ligand vancomycin to enable targeted antimicrobial photodynamic therapy. The riboflavin-vancomycin conjugate proved to be a potent and versatile antibacterial agent, enabling the rapid, light-mediated, killing of MRSA and VRE with no significant off-target effects. The attachment of riboflavin on vancomycin also led to an increase in antibiotic activity against S. aureus and VRE. Simultaneously, we evidenced for the first time that the flavin subunit undergoes an efficient photoinduced bond cleavage reaction to release vancomycin, thereby acting as a photoremovable protecting group with potential applications in drug delivery

Increasing adolescent self-esteem: a focus on wellness and process

ix, 116 leaves : ill. ; 28 cmThe project presents an overview of a psychoeducational group therapy program designed to increase self-esteem in adolescents and integrates the indivisible self model of wellness (Myers & Sweeney, 2005b) and process work. Adolescence is a time often marked by low levels of self-esteem and identity conflict. The indivisible self model of wellness provides a framework for exploring different aspects of identity, with the goal of increasing self-esteem. In addition, process work has been found to be an indispensable component of effective counselling groups (Yalom & Leszcz, 2005). Nevertheless, the focus in psychoeducational groups is often on teaching (Corey, Corey, & Corey, 2010). As such, this project not only outlines a group therapy program to assist practitioners in increasing adolescent self-esteem, it also outlines one way to integrate process work into a psychoeducational group. This project contains both a theoretical and applied component. An overview of the literature on adolescent self-esteem and the indivisible self model of wellness is presented. This is followed by an overview of guidelines counsellors can utilize to assist in the integration of process work into psychoeducational counselling groups. The applied component of this project is a manuscript that outlines the proposed group therapy program

Red-Shifted Environmental Fluorophores and Their Use for the Detection of Gram-Negative Bacteria

Two novel, water-soluble, merocyanine fluorophores were readily prepared by microwave-assisted synthesis. Full optical characterization was performed in a series of protic and aprotic solvents, and the dyes displayed fluorescence in the red region with up to a 20-fold decrease in brightness in water, demonstrating a strong environmental sensitivity hereby termed as solvato-fluorogenicity (to distinguish from solvatochromism). Shorter fluorescent lifetimes were also measured in water, which confirmed this character. These dyes were conjugated to a modified polymyxin scaffold that allowed fluorescence “switch-on” upon binding to Gram-negative bacterial membranes, and selective fluorescence detection of bacteria in a wash-free protocol