Intracochlear Perfusion of Pneumolysin, a Pneumococcal Protein, Rapidly Abolishes Auditory Potentials in the Guinea Pig Cochlea

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Abstract
Objective —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. Material and Methods —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. Results —Intracochlear perfusion of pneumolysin (10 μg/50 μl) 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 μg/50 μl), a selective and earlier effect on inner hair cells was observed. Conclusions —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.