H2S-releasing amphiphilic dipeptide hydrogels are potent S. aureus biofilm disruptors

Abstract

As a gasotransmitter, hydrogen sulfide (H₂S) has been studied to treat wounds and inflammation, but its potential antimicrobial effects in this context have not been evaluated. An H₂S-releasing dipeptide hydrogel (S-FE), and several non-H₂S-releasing control dipeptides, (C-FE, C-GE, FBA-FE, and FE where S = S-aroylthiooxime, an H₂S donor; C = control, an oxime incapable of H₂S release; FBA = 4-formylbenzamide, also incapable of H₂S release; and E, F, G = glutamic acid, phenylalanine, and glycine, respectively), were studied to correlate differences in their chemical structures and H₂S-releasing abilities with their antimicrobial effects on Staphylococcus aureus bacteria. Dipeptides with Phe (S-FE, C-FE, and FE) self-assembled into nanoribbons in water and displayed β-sheet formation and enhanced fluorescence, while the other two dipeptides (FBA-FE and C-GE) did not form assemblies in water. In vitro experiments with Staphylococcus aureus, which is a commonly found bacterium associated with wounds, showed significant antimicrobial effects from some of the dipeptides. Dipeptide S-FE inhibited bacterial growth more effectively than any of the controls, thereby limiting biofilm formation or disrupting established biofilms. These antimicrobial H₂S-releasing dipeptide hydrogels provide a promising new approach to treat wound infections.