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Coagulase-negative staphylococci release a purine analog that inhibits Staphylococcus aureus virulence

Author

Listed:
  • Denny Chin

    (University of Western Ontario)

  • Mariya I. Goncheva

    (University of Western Ontario)

  • Ronald S. Flannagan

    (University of Western Ontario)

  • Shayna R. Deecker

    (MaRS Centre)

  • Veronica Guariglia-Oropeza

    (University of Western Ontario)

  • Alexander W. Ensminger

    (MaRS Centre
    MaRS Centre)

  • David E. Heinrichs

    (University of Western Ontario)

Abstract

Coagulase-negative staphylococci and Staphylococcus aureus colonize similar niches in mammals and conceivably compete for space and nutrients. Here, we report that a coagulase-negative staphylococcus, Staphylococcus chromogenes ATCC43764, synthesizes and secretes 6-thioguanine (6-TG), a purine analog that suppresses S. aureus growth by inhibiting de novo purine biosynthesis. We identify a 6-TG biosynthetic gene cluster in S. chromogenes and other coagulase-negative staphylococci including S. epidermidis, S. pseudintermedius and S. capitis. Recombinant S. aureus strains harbouring this operon produce 6-TG and, when used in subcutaneous co-infections in mice with virulent S. aureus USA300, protect the host from necrotic lesion formation. Used prophylactically, 6-TG reduces necrotic skin lesions in mice infected with USA300, and this effect is mediated by abrogation of toxin production. RNAseq analyses reveal that 6-TG downregulates expression of genes coding for purine biosynthesis, the accessory gene regulator (agr) and ribosomal proteins in S. aureus, providing an explanation for its effect on toxin production.

Suggested Citation

  • Denny Chin & Mariya I. Goncheva & Ronald S. Flannagan & Shayna R. Deecker & Veronica Guariglia-Oropeza & Alexander W. Ensminger & David E. Heinrichs, 2021. "Coagulase-negative staphylococci release a purine analog that inhibits Staphylococcus aureus virulence," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-22175-3
    DOI: 10.1038/s41467-021-22175-3
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    Cited by:

    1. Bingyan Wei & Tao Zhang & Pengyu Wang & Yihui Pan & Jiahui Li & Weizhong Chen & Min Zhang & Quanjiang Ji & Wenjuan Wu & Lefu Lan & Jianhua Gan & Cai-Guang Yang, 2022. "Anti-infective therapy using species-specific activators of Staphylococcus aureus ClpP," Nature Communications, Nature, vol. 13(1), pages 1-16, December.

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