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

被引：113

作者：

Blake, Kimbria J. ^{[1
]}

Baral, Pankaj ^{[1
]}

Voisin, Tiphaine ^{[1
]}

Lubkin, Ashira ^{[2
]}

Pinho-Ribeiro, Felipe Almeida ^{[1
]}

Adams, Kelsey L. ^{[1
]}

Roberson, David P. ^{[3
,4
]}

Ma, Yuxin C. ^{[1
]}

Otto, Michael ^{[5
]}

Woolf, Clifford J. ^{[3
,4
]}

Torres, Victor J. ^{[2
]}

Chiu, Isaac M. ^{[1
]}

机构：

[1] Harvard Med Sch, Div Immunol, Dept Microbiol & Immunobiol, Boston, MA 02115 USA

[2] NYU, Sch Med, Dept Microbiol, New York, NY 10016 USA

[3] Harvard Med Sch, Dept Neurobiol, Boston, MA 02115 USA

[4] Boston Childrens Hosp, FM Kirby Neurobiol Ctr, Boston, MA 02155 USA

[5] NIAID, Pathogen Mol Genet Sect, Lab Bacteriol, NIH, Bethesda, MD 20814 USA

来源：

NATURE COMMUNICATIONS | 2018年 / 9卷

基金：

美国国家卫生研究院;

关键词：

PHENOL-SOLUBLE MODULINS; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; ALPHA-TOXIN; INTRAOSSEOUS INJECTION; VIRULENCE DETERMINANTS; ANESTHETIC EFFICACY; CHEMOKINE RECEPTORS; IONIC CHANNELS; INFECTION; INFLAMMATION;

D O I：

10.1038/s41467-017-02448-6

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：15

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