Intracochlear perfusion of pneumolysin, a pneumococcal protein, rapidly abolishes auditory potentials in the Guinea pig cochlea.
Acta Oto-Laryngologica. 2004-11-01; 124(9): 1000-1007
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1. Acta Otolaryngol. 2004 Nov;124(9):1000-7.
Intracochlear perfusion of pneumolysin, a pneumococcal protein, rapidly abolishes
auditory potentials in the Guinea pig cochlea.
Skinner LJ(1), Beurg M, Mitchell TJ, Darrouzet V, Aran JM, Dulon D.
(1)Laboratoire de Biologie Cellulaire et Moléculaire de l’Audition Université de
Bordeaux 2, CHU Hôpital Pellegrin EA 3665 Bordeaux, France.
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 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
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.
PMID: 15513541 [Indexed for MEDLINE]