S-Se-S type molecule: A bactericidal promoter against H<sub>2</sub>S-induced antibiotic resistance

<p>The hydrogen sulfide (H₂S)-induced defense system is a crucial bacterial pathway that leads to antibiotic resistance. Herein, a unique S-Se-S molecule, namely, 2,2’-(selenobis(sulfanediyl))diacetic acid (Se-Acid), is first reported to relieve H₂S-induced antibiotic resistance by acting as a hydrogen selenide (H₂Se) donor. The S-Se-S molecular structure was formed using the carboxyl terminal as an electron acceptor. After being endocytosed by cells, Se-Acid effectively released H₂Se molecules by reacting with glutathione (GSH). The released H₂Se increased the endocytosis of antibiotics by promoting bacterial membrane permeability. Moreover, H₂Se effectively reactivated the bacterial respiratory flux by functioning as an H₂S disguiser. The synergistic effect of Se-Acid and Gentamicin (Gm) on H₂S-induced antibiotic-resistant MRSA was proven on MRSA^S+ wound infection model. Our results establish S-Se-S type molecules as potential tools for addressing the challenge of H₂S-induced antibiotic resistance and reducing the risk of antibiotic resistance.</p>