S-Se-S type molecule: A bactericidal promoter against H2S-induced antibiotic resistance
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GRAPHICAL ABSTRACT
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PUBLIC SUMMARY
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A unique and stable S-Se-S molecule structure (Se-Acid) was first synthesized and verified.
A clear reaction mechanism was illustrated about the triggered release of H2Se from Se-Acid by glutathione.
H2Se relieved antibiotic resistance through promoting membrane permeability and reactivating respiratory flux.
S-Se-S type molecule could play key role for addressing the challenge of H2S-induced antibiotic resistance.
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ABSTRACT
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 MRSAS+ 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. -
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REFERENCES
[1] Darby, E.M., Trampari, E., Siasat, P., et al. (2023). Molecular mechanisms of antibiotic resistance revisited. Nat. Rev. Microbiol. 21: 280−295. DOI: 10.1038/s41579-022-00820-y. [2] Larsson, D.G.J. and Flach, C.-F. (2022). Antibiotic resistance in the environment. Nat. Rev. Microbiol. 20: 257−269. DOI: 10.1038/s41579-021-00649-x. [3] Stower, H. (2020). Antibiotic tolerance leads to antibiotic resistance. Nat. Med. 26: 163−163. DOI: 10.1038/s41591-020-0778-7. [4] Zha, Y., Chen, C., Jiao, Q., et al. (2024). Comprehensive profiling of antibiotic resistance genes in diverse environments and novel function discovery. The Innovation Life 2: 100054. DOI: 10.59717/j.xinn-life.2024.100054. [5] Darby, E.M., Trampari, E., Siasat, P., et al. (2023). Molecular mechanisms of antibiotic resistance revisited. Nat. Rev. Microbiol. 21: 280−295. DOI: 10.1038/s41579-022-00820-y. [6] Blair, J.M.A., Webber, M.A., Baylay, A.J., et al. (2015). Molecular mechanisms of antibiotic resistance. Nat. Rev. Microbiol. 13: 42−51. DOI: 10.1038/nrmicro3380. [7] Michiels, J.E., Van den Bergh, B., Verstraeten, N., et al. (2016). Molecular mechanisms and clinical implications of bacterial persistence. Drug Resist. Updat. 29: 76−89. DOI: 10.1016/j.drup.2016.10.002. [8] Kimura, H. (2015). Signaling of hydrogen sulfide and polysulfides. Antioxid. Redox Signal. 22: 347−349. DOI: 10.1089/ars.2014.6082. [9] Shatalin, K., Shatalina, E., Mironov, A., et al. (2011). H2S: A universal defense against antibiotics in bacteria. Science 334: 986−990. DOI: 10.1126/science.1209855. [10] Shukla, P., Khodade, V.S., SharathChandra, M., et al. (2017). “On demand” redox buffering by H2S contributes to antibiotic resistance revealed by a bacteria-specific H2S donor. Chem. Sci. 8: 4967−4972. DOI: 10.1039/C7SC00873B. [11] Kimura H. (2015). Physiological roles of hydrogen sulfide and polysulfides. Handb. Exp. Pharmacol. 230: 61−81. DOI: 10.1007/978-3-319-18144-8_3. [12] Shatalin, K., Nuthanakanti, A., Kaushik, A., et al. (2021). Inhibitors of bacterial H2S biogenesis targeting antibiotic resistance and tolerance. Science 372: 1169−1175. DOI: 10.1126/science.abd8377. [13] Xie, M., Gao, M., Yun, Y., et al. (2023). Antibacterial nanomaterials: Mechanisms, impacts on antimicrobial resistance and design principles. Angew. 62: e202217345. DOI: 10.1002/anie.202217345. [14] Zhang, S., Yang, H., Wang, M., et al. (2023). Immunomodulatory biomaterials against bacterial infections: Progress, challenges, and future perspectives. The Innovation 4: 100503. DOI: 10.1016/j.xinn.2023.100503. [15] Makabenta, J.M.V., Nabawy, A., Li, C.-H., et al. (2021). Nanomaterial-based therapeutics for antibiotic-resistant bacterial infections. Nat. Rev. Microbiol. 19: 23−36. DOI: 10.1038/s41579-020-0420-1. [16] Cupp-Sutton, K.A., and Ashby, M.T. (2016). Biological chemistry of hydrogen selenide. Antioxidants 5: 42. DOI: 10.3390/antiox5040042. [17] Mapelli, V., Hillestrøm, P.R., Patil, K., et al. (2012). The interplay between sulphur and selenium metabolism influences the intracellular redox balance in Saccharomyces cerevisiae. FEMS Yeast Res. 12: 20−32. DOI: 10.1111/j.1567-1364.2011.00757.x. [18] Xia, J., Li, T., Lu, C., et al. (2018). Selenium-containing polymers: Perspectives toward diverse applications in both adaptive and biomedical materials. Macromolecules 51: 7435−7455. DOI: 10.1021/acs.macromol.8b01597. [19] Kushkevych, I., Cejnar, J., Treml, J., et al. (2020). Recent advances in metabolic pathways of sulfate reduction in intestinal bacteria. Cells 9: 698. DOI: 10.3390/cells9030698. [20] Wolf, P.G., Cowley, E.S., Breister, A., et al. (2022). Diversity and distribution of sulfur metabolic genes in the human gut microbiome and their association with colorectal cancer. Microbiome 10: 64. DOI: 10.1186/s40168-022-01242-x. [21] Weekley, C.M. and Harris, H.H. (2013). Which form is that? The importance of selenium speciation and metabolism in the prevention and treatment of disease. Chem. Soc. Rev. 42: 8870. DOI: 10.1039/c3cs60272a. [22] Kang, X., Huang, H., Jiang, C., et al. (2022). Cysteine-activated small-molecule H2Se donors inspired by synthetic H2S donors. J. Am. Chem. Soc. 144: 3957−3967. DOI: 10.1021/jacs.1c12006. [23] Newton, T.D., and Pluth, M.D. (2019). Development of a hydrolysis-based small-molecule hydrogen selenide (H2Se) donor. Chem. Sci. 10: 10723−10727. DOI: 10.1039/C9SC04616J. [24] Yang, Y., Sun, B., Zuo, S., et al. (2020). Trisulfide bond-mediated doxorubicin dimeric prodrug nanoassemblies with high drug loading, high self-assembly stability, and high tumor selectivity. Sci. Adv. 6: eabc1725. DOI: 10.1126/sciadv.abc1725. [25] Vestergaard, M., Bald, D., and Ingmer, H. (2022). Targeting the ATP synthase in bacterial and fungal pathogens: Beyond Mycobacterium tuberculosis. J. Glob. Antimicrob. Resist. 29: 29−41. DOI: 10.1016/j.jgar.2022.01.026. [26] Lamprecht, D.A., Finin, P.M., Rahman, M.A., et al. (2016). Turning the respiratory flexibility of Mycobacterium tuberculosis against itself. Nat. Commun. 7: 1−14. DOI: 10.1038/ncomms12393. [27] Liu, Z., Guo, K., Yan, L., et al. (2023). Janus nanoparticles targeting extracellular polymeric substance achieve flexible elimination of drug-resistant biofilms. Nat. Commun. 14: 5132. DOI: 10.1038/s41467-023-40830-9. -
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Liu M., Bu F., Li G., et al., (2024). S-Se-S type molecule: A bactericidal promoter against H2S-induced antibiotic resistance. The Innovation Life 2(3): 100076. https://doi.org/10.59717/j.xinn-life.2024.100076
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Liu M., Bu F., Li G., et al., (2024). S-Se-S type molecule: A bactericidal promoter against H2S-induced antibiotic resistance. The Innovation Life 2(3): 100076. https://doi.org/10.59717/j.xinn-life.2024.100076
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Figure 1.
Synthesis and basic characterization of S-Se-S type molecules
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Figure 2.
The mechanisms underlying the release of H2Se from Se-Acid in response to GSH
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Figure 3.
The synergistic bactericidal effects of Se-Acid and Gm
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Figure 4.
The mechanism of Se-Acid against H2S-induced antibiotic resistance
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Figure 5.
In vivo anti-infection effects of Se-Acid against H2S-induced antibiotic resistance
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