Skinner Liam J, Beurg Maryline, Mitchell Timothy J, Darrouzet Vincent, Aran Jean-Marie, Dulon Didier
Laboratoire de Biologie Cellulaire et Moléculaire de l'Audition Université de Bordeaux 2, CHU Hôpital Pellegrin EA 3665 Bordeaux, France.
Acta Otolaryngol. 2004 Nov;124(9):1000-7. doi: 10.1080/00016480410017125.
Bacterial meningitis and chronic suppurative otitis media caused by Streptococcus pneumoniae are associated with considerable otological morbidity. Specifically, sensorineural hearing loss is a permanent sequela in a third of those who contract pneumococcal meningitis. Pneumolysin, a pneumococcal protein, has been implicated as one of the main virulence/cytotoxic factors. Its pathogenicity is intimately dependent on an ability to form transmembrane pores on binding with cholesterol in target tissues.
We perfused wild-type pneumolysin, at a number of different concentrations, into the guinea pig cochlea and used electrocochleography to characterize the effects of this cytolytic exotoxin in the organ of Corti.
Intracochlear perfusion of pneumolysin (10 microg/50 microl) reduced the compound action potential of the auditory nerve within seconds. The cochlear microphonics (f1=8 kHz, f2=9.68 kHz) and their distortion product (2f1-f2) were also reduced, albeit in a slightly less dramatic fashion. At lower concentrations (1 microg/50 microl), a selective and earlier effect on inner hair cells was observed.
These results clearly show that significant ototoxicity ensues when sensory cells of the organ of Corti are exposed to pneumolysin (and complete cochlear death when the concentration is high enough). Toxicity is dose-dependent and appears to be site-sensitive. This may have implications for any possible future protective strategies against pneumococcal disease in the ear.
肺炎链球菌引起的细菌性脑膜炎和慢性化脓性中耳炎会导致相当严重的耳科疾病。具体而言，感音神经性听力损失是三分之一患肺炎球菌性脑膜炎患者的永久性后遗症。肺炎溶血素是一种肺炎球菌蛋白，被认为是主要的毒力/细胞毒性因子之一。其致病性密切依赖于与靶组织中的胆固醇结合形成跨膜孔的能力。
我们将多种不同浓度的野生型肺炎溶血素灌注到豚鼠耳蜗中，并用电耳蜗图来表征这种溶细胞外毒素在柯蒂氏器中的作用。
耳蜗内灌注肺炎溶血素（10微克/50微升）在数秒内降低了听神经的复合动作电位。耳蜗微音器电位（f1 = 8千赫，f2 = 9.68千赫）及其畸变产物（2f1 - f2）也有所降低，尽管程度稍小。在较低浓度（1微克/50微升）时，观察到对内毛细胞有选择性且更早出现的影响。
这些结果清楚地表明，当柯蒂氏器的感觉细胞暴露于肺炎溶血素时会产生明显的耳毒性（当浓度足够高时会导致整个耳蜗死亡）。毒性具有剂量依赖性，且似乎对部位敏感。这可能对未来任何针对耳部肺炎球菌疾病的可能保护策略都有影响。
