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Staphylococcus aureus produces pain through pore-forming toxins and neuronal TRPV1 that is silenced by QX-314

Author

Listed:
  • Kimbria J. Blake

    (Division of Immunology, Harvard Medical School)

  • Pankaj Baral

    (Division of Immunology, Harvard Medical School)

  • Tiphaine Voisin

    (Division of Immunology, Harvard Medical School)

  • Ashira Lubkin

    (New York University School of Medicine)

  • Felipe Almeida Pinho-Ribeiro

    (Division of Immunology, Harvard Medical School)

  • Kelsey L. Adams

    (Division of Immunology, Harvard Medical School)

  • David P. Roberson

    (Harvard Medical School
    F.M. Kirby Neurobiology Center, Boston Children’s Hospital)

  • Yuxin C. Ma

    (Division of Immunology, Harvard Medical School)

  • Michael Otto

    (Pathogen Molecular Genetics Section, Laboratory of Bacteriology, National Institute of Allergy and Infectious Disease, National Institutes of Health)

  • Clifford J. Woolf

    (Harvard Medical School
    F.M. Kirby Neurobiology Center, Boston Children’s Hospital)

  • Victor J. Torres

    (New York University School of Medicine)

  • Isaac M. Chiu

    (Division of Immunology, Harvard Medical School)

Abstract

The hallmark of many bacterial infections is pain. The underlying mechanisms of pain during live pathogen invasion are not well understood. Here, we elucidate key molecular mechanisms of pain produced during live methicillin-resistant Staphylococcus aureus (MRSA) infection. We show that spontaneous pain is dependent on the virulence determinant agr and bacterial pore-forming toxins (PFTs). The cation channel, TRPV1, mediated heat hyperalgesia as a distinct pain modality. Three classes of PFTs—alpha-hemolysin (Hla), phenol-soluble modulins (PSMs), and the leukocidin HlgAB—directly induced neuronal firing and produced spontaneous pain. From these mechanisms, we hypothesized that pores formed in neurons would allow entry of the membrane-impermeable sodium channel blocker QX-314 into nociceptors to silence pain during infection. QX-314 induced immediate and long-lasting blockade of pain caused by MRSA infection, significantly more than lidocaine or ibuprofen, two widely used clinical analgesic treatments.

Suggested Citation

  • Kimbria J. Blake & Pankaj Baral & Tiphaine Voisin & Ashira Lubkin & Felipe Almeida Pinho-Ribeiro & Kelsey L. Adams & David P. Roberson & Yuxin C. Ma & Michael Otto & Clifford J. Woolf & Victor J. Torr, 2018. "Staphylococcus aureus produces pain through pore-forming toxins and neuronal TRPV1 that is silenced by QX-314," Nature Communications, Nature, vol. 9(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-017-02448-6
    DOI: 10.1038/s41467-017-02448-6
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    Cited by:

    1. Chen Huang & Pei-Yi Sun & Yiming Jiang & Yuandong Liu & Zhichao Liu & Shao-Ling Han & Bao-Shan Wang & Yong-Xin Huang & An-Ran Ren & Jian-Fei Lu & Qin Jiang & Ying Li & Michael X. Zhu & Zhirong Yao & Y, 2024. "Sensory ASIC3 channel exacerbates psoriatic inflammation via a neurogenic pathway in female mice," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    2. Diane Aguilar & Fengli Zhu & Antoine Millet & Nicolas Millet & Patrizia Germano & Joseph Pisegna & Omid Akbari & Taylor A. Doherty & Marc Swidergall & Nicholas Jendzjowsky, 2024. "Sensory neurons regulate stimulus-dependent humoral immunity in mouse models of bacterial infection and asthma," Nature Communications, Nature, vol. 15(1), pages 1-18, December.

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