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Updated: Mar 3, 2026
Primary Culture and Plasmid Electroporation of the Murine Organ of Corti.
Published on: February 4, 2010
Streptococcus pneumoniae-induced ototoxicity in organ of Corti explant cultures
Michael Perny1, Magdalena Solyga2, Denis Grandgirard3
1Neuroinfection Laboratory, Institute for Infectious Diseases, University of Bern, Switzerland; Inner Ear Research Laboratory, Department of Otorhinolaryngology, Head& Neck Surgery, Inselspital Bern and Department of Clinical Research, University of Bern, Switzerland; Cluster for Regenerative Neuroscience, Department of Clinical Research, University of Bern, Switzerland.
Abstract:
Hearing loss remains the most common long-term complication of pneumococcal meningitis (PM) reported in up to 30% of survivors. Streptococcus pneumoniae have been shown to possess different ototoxic properties. Here we present a novel ex vivo experimental setup to examine in detail the pattern of hair cell loss upon exposure to different S. pneumoniae strains, therefore recapitulating pathogen derived aspects of PM-induced hearing loss. Our results show a higher susceptibility towards S. pneumoniae-induced cochlear damage for outer hair cells (OHC) compared to inner hair cells (IHC), which is consistent with in vivo data. S. pneumoniae-induced hair cell loss was both time and dose-dependent. Moreover, we have found significant differences in the level of cell damage between tissue from the basal and the apical turns. This shows that the higher vulnerability of hair cells located at high frequency regions observed in vivo cannot be explained solely by the spatial organisation and bacterial infiltration from the basal portion of the cochlea. Using a wild type D39 strain and a mutant defective for the pneumolysin (PLY) gene, we also have shown that the toxin PLY is an important factor involved in ototoxic damages. The obtained results indicate that PLY can cause both IHC and OHC loss. Finally, we are reporting here for the first time a higher vulnerability of HC located at the basal and middle cochlear region to pneumolysin-induced damage. The detailed description of the susceptibility of hair cells to Streptococcus pneumoniae provided in this report can in the future determine the choice and the development of novel otoprotective therapies during pneumococcal meningitis.
Insights
Pneumococcal meningitis survivors often experience hearing loss. This study reveals Streptococcus pneumoniae damages cochlear hair cells, particularly outer hair cells, with the toxin pneumolysin being a key factor in this ototoxicity.
Area of Science:
- Ototoxicity and neuroinflammation
- Microbiology and infectious diseases
- Auditory neuroscience
Background:
- Hearing loss is a common sequela of pneumococcal meningitis (PM), affecting up to 30% of survivors.
- Streptococcus pneumoniae exhibits ototoxic properties contributing to PM-induced hearing damage.
- Understanding pathogen-derived mechanisms of hearing loss is crucial for developing otoprotective therapies.
Purpose of the Study:
- To investigate the pattern of cochlear hair cell loss induced by different Streptococcus pneumoniae strains using a novel ex vivo model.
- To elucidate the role of bacterial factors, specifically pneumolysin (PLY), in pathogen-induced ototoxicity.
- To determine the differential susceptibility of hair cell populations within the cochlea to S. pneumoniae and its toxins.
Main Methods:
- Development of a novel ex vivo experimental setup to expose cochlear tissue to S. pneumoniae strains.
- Quantitative analysis of hair cell loss (inner hair cells [IHCs] and outer hair cells [OHCs]) in response to bacterial exposure.
- Comparison of damage patterns between wild-type and pneumolysin-deficient (PLY mutant) S. pneumoniae strains.
Main Results:
- Outer hair cells (OHCs) demonstrated higher susceptibility to S. pneumoniae-induced damage than inner hair cells (IHCs).
- Hair cell loss was dose- and time-dependent, with significant regional differences observed between basal and apical cochlear turns.
- Pneumolysin (PLY) was identified as a critical ototoxic factor, causing both IHC and OHC loss, with a notable vulnerability in the basal and middle cochlear regions.
Conclusions:
- The ex vivo model effectively recapitulates S. pneumoniae-induced cochlear damage, highlighting OHC vulnerability and regional susceptibility.
- Pneumolysin is a significant contributor to S. pneumoniae ototoxicity, affecting hair cells across different cochlear regions.
- These findings provide a basis for developing targeted otoprotective strategies against hearing loss in pneumococcal meningitis.
