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

Biomater Sci. 2020 May 7;8(9):2564-2576. doi: 10.1039/d0bm00241k. Epub 2020 Mar 31.

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.

MeSH terms

  • Anti-Bacterial Agents / administration & dosage*
  • Biofilms / drug effects
  • Dipeptides / administration & dosage*
  • Dipeptides / chemistry
  • Hydrogels / administration & dosage*
  • Hydrogen Sulfide / chemistry*
  • Staphylococcus aureus / drug effects*
  • Staphylococcus aureus / physiology

Substances

  • Anti-Bacterial Agents
  • Dipeptides
  • Hydrogels
  • Hydrogen Sulfide