A Role for Pneumolysin but Not Neuraminidase in the Hearing Loss and Cochlear Damage Induced by Experimental Pneumococcal Meningitis in Guinea Pigs

We investigated the roles of pneumolysin and neuraminidase in the pathogenesis of deafness and cochlear damage during experimental pneumococcal meningitis. Anesthetized guinea pigs were inoculated intracranially with 7.5 log 10 CFU of either (i) wild-type Streptococcus pneumoniae D39 (n ‫؍‬ 8), (ii) PLN-A, a defined isogenic derivative of D39 deficient in pneumolysin (n ‫؍‬ 5), or (iii) ⌬NA1, a new derivative of D39 deficient in neuraminidase constructed by insertion-duplication mutagenesis of the nanA gene (n ‫؍‬ 5). To quantify hearing loss, the auditory nerve compound action potential evoked by a tone pulse was recorded from the round window membrane of the cochlea every 3 h for 12 h. The organ of Corti was intravitally fixed for subsequent examination by high-resolution scanning and transmission electron microscopy. All animals sustained similar meningeal inflammatory responses. PLN-A induced significantly less hearing loss than D39 over the frequency range of 3 to 10 kHz. Levels of mean hearing loss at 10 kHz 12 h postinoculation were as follows: D39, 50 dB