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 path ogenesis of deafness and cochlear damage during experimental pneumococ cal meningitis. Anesthetized guinea pigs were inoculated intracraniall y with 7.5 log(10) CFU of either (i) wild-type Streptococcus pneumonia e D39 (n = 8), (ii) PLN-A, a defined isogenic derivative of D39 defici ent in pneumolysin (n = 5), or (iii) Delta NA1, a new derivative of D3 9 deficient in neuraminidase constructed by insertion-duplication muta genesis of the nanA gene (n = 5). To quantify hearing loss, the audito ry 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 h igh-resolution scanning and transmission electron microscopy. All anim als 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; Delta NA1, 52 dB (P = 0.76 versus D39), and PLN-A, 12 dB (P < 0.0001 versus D39). The mean rates of hearing lo ss at 10 kHz were 4.4 dB/h for D39, 4.3 dB/h for Delta NA1, and just 1 .0 dB/h for PLN-A (P < 0.0001 versus D39). Suppurative labyrinthitis w as universal. PLN-A induced the accumulation of less protein in the ce rebrospinal fluid (P = 0.04 versus D39). Infection with D39 and Delta NA1 induced significant damage to the reticular lamina, the sensory ha ir cells, and supporting cells of the organ of Corti. By contrast, aft er infection with PLN-A, the organ of Corti appeared virtually intact. Pneumolysin seems to be the principal cause of cochlear damage in thi s model of meningogenic deafness. No clear pathogenic role was demonst rated for neuraminidase.