21:T43f,Antimicrobial photodynamic therapy (APDT) has gained increased attention because of its broad spectrum activity and lower likelihood to elicit bacterial resistance. Although many photosensitizers excel at eradicating Gram-positive bacterial infections, they are generally less potent when utilized against Gram-negative bacteria. We hypothesized that conjugating the DNA-targeting, antimicrobial peptide buforin II to a metal-based photosensitizer would result in a potent APDT agent. Herein, we present the synthesis and characterization of a buforin II-[Ru(bpy)₃]²⁺ bioconjugate (1). The submicromolar activity of 1 against the multidrug-resistant strains Escherichia coli AR 0114 and Acinetobacter baumannii Naval-17 indicates strong synergy between the ruthenium complex and buforin II. Our mechanistic studies point to an increased rate of DNA damage by 1 compared to [Ru(bpy)₃]²⁺. These results suggest that conjugating metal complexes to antimicrobial peptides can lead to potent antimicrobial agents.22:T4a4,Tunicates have been used as primitive models for understanding cell-mediated and humoral immunity. Clavanin A (ClavA) is one member of a family of antimicrobial peptides produced by the solitary tunicate Styela clava. In this work, we demonstrate that ClavA utilizes Zn²⁺ ions to potentiate its antimicrobial activity not only by reducing the concentration at which the peptide inhibits the growth of bacteria but also by increasing the rate of killing. Membrane depolarization, β-galactosidase leakage, and potassium leakage assays indicate that ClavA is membrane active, forms small pores, but induces cell death by targeting an intracellular component. ClavA and ClavA-Zn²⁺ added to Escherichia coli and imaged by confocal microscopy translocate across the cell membrane. E. coli mutants lacking the functional Zn²⁺ import system are less susceptible to ClavA, suggesting that the synergistic activity between ClavA and Zn²⁺ has a cytoplasmic target, which is further supported by its nucleolytic activity. Overall, these studies identify a remarkable new mechanism by which zinc contributes to the immune response in the tunicate S. clava.23:T784,

	Year	Citations

About