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Transcription tuned by S-nitrosylation underlies a mechanism for Staphylococcus aureus to circumvent vancomycin killing

Author

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  • Xueqin Shu

    (Division of Life Sciences and Medicine, University of Science and Technology of China)

  • Yingying Shi

    (Division of Life Sciences and Medicine, University of Science and Technology of China)

  • Yi Huang

    (Division of Life Sciences and Medicine, University of Science and Technology of China)

  • Dan Yu

    (Beijing Pediatric Research Institute, Beijing Children’s Hospital, Capital Medical University, Key Laboratory of Major Diseases in Children, Ministry of Education, National Center for Children’s Health)

  • Baolin Sun

    (Division of Life Sciences and Medicine, University of Science and Technology of China
    University of Science and Technology of China
    Hefei National Laboratory for Physical Sciences at Microscale)

Abstract

Treatment of Staphylococcus aureus infections is a constant challenge due to emerging resistance to vancomycin, a last-resort drug. S-nitrosylation, the covalent attachment of a nitric oxide (NO) group to a cysteine thiol, mediates redox-based signaling for eukaryotic cellular functions. However, its role in bacteria is largely unknown. Here, proteomic analysis revealed that S-nitrosylation is a prominent growth feature of vancomycin-intermediate S. aureus. Deletion of NO synthase (NOS) or removal of S-nitrosylation from the redox-sensitive regulator MgrA or WalR resulted in thinner cell walls and increased vancomycin susceptibility, which was due to attenuated promoter binding and released repression of genes involved in cell wall metabolism. These genes failed to respond to H2O2-induced oxidation, suggesting distinct transcriptional responses to alternative modifications of the cysteine residue. Furthermore, treatment with a NOS inhibitor significantly decreased vancomycin resistance in S. aureus. This study reveals that transcriptional regulation via S-nitrosylation underlies a mechanism for NO-mediated bacterial antibiotic resistance.

Suggested Citation

  • Xueqin Shu & Yingying Shi & Yi Huang & Dan Yu & Baolin Sun, 2023. "Transcription tuned by S-nitrosylation underlies a mechanism for Staphylococcus aureus to circumvent vancomycin killing," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-37949-0
    DOI: 10.1038/s41467-023-37949-0
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