Staphylococcus aureus produces pain through pore-forming toxins and neuronal TRPV1 that is silenced by QX-314
| Autor: | Michael Otto, Kelsey L. Adams, Ashira Lubkin, Victor J. Torres, David Roberson, Kimbria J. Blake, Clifford J. Woolf, Tiphaine Voisin, Yuxin C. Ma, Isaac M. Chiu, Felipe A. Pinho-Ribeiro, Pankaj Baral |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Methicillin-Resistant Staphylococcus aureus
0301 basic medicine Science Bacterial Toxins Analgesic TRPV1 Leukocidin Pain TRPV Cation Channels General Physics and Astronomy Pharmacology medicine.disease_cause Article General Biochemistry Genetics and Molecular Biology Mice 03 medical and health sciences 0302 clinical medicine Sodium channel blocker medicine Animals Anesthetics Local lcsh:Science Pathogen Neurons Multidisciplinary business.industry fungi Lidocaine food and beverages General Chemistry Staphylococcal Infections Ibuprofen 3. Good health Mice Inbred C57BL 030104 developmental biology Staphylococcus aureus Gene Knockdown Techniques Nociceptor lcsh:Q business 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Nature Communications, Vol 9, Iss 1, Pp 1-15 (2018) Nature Communications |
| ISSN: | 2041-1723 |
| Popis: | 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. Bacterial infection can cause pain but the underlying mechanism is unclear. This study shows pain induced in mice by methicillin-resistant Staphylococcus aureus infection is mediated by bacterial pore-forming toxins, and a sodium channel blocker QX-314 can alleviate infection-associated pain. |
| Databáze: | OpenAIRE |
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