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 log10 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) deltaNA1, 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; deltaNA1, 52 dB (P = 0.76 versus D39), and PLN-A, 12 dB (P < 0.0001 versus D39). The mean rates of hearing loss at 10 kHz were 4.4 dB/h for D39, 4.3 dB/h for deltaNA1, and just 1.0 dB/h for PLN-A (P < 0.0001 versus D39). Suppurative labyrinthitis was universal. PLN-A induced the accumulation of less protein in the cerebrospinal fluid (P = 0.04 versus D39). Infection with D39 and deltaNA1 induced significant damage to the reticular lamina, the sensory hair cells, and supporting cells of the organ of Corti. By contrast, after infection with PLN-A, the organ of Corti appeared virtually intact. Pneumolysin seems to be the principal cause of cochlear damage in this model of meningogenic deafness. No clear pathogenic role was demonstrated for neuraminidase.
Winter
A J
AJ
Department of Infection, University of Birmingham, United Kingdom.
Comis
S D
SD
Osborne
M P
MP
Tarlow
M J
MJ
Stephen
J
J
Andrew
P W
PW
Hill
J
J
Mitchell
T J
TJ
D000818:Animals; D001426:Bacterial Proteins; D003051:Cochlea / Q000648:ultrastructure*; D003638:Deafness / Q000209:etiology*; D005260:Female; D006168:Guinea Pigs; D008297:Male; D008586:Meningitis, Pneumococcal / Q000150:complications* / Q000473:pathology; D008855:Microscopy, Electron, Scanning; D009439:Neuraminidase / Q000633:toxicity*; D013301:Streptolysins / Q000633:toxicity*
D001426:Bacterial Proteins; D013301:Streptolysins; C032290:plY protein, Streptococcus pneumoniae; D009439:Neuraminidase