Zinc protection against pneumolysin toxicity on rat cochlear hair cells.
Streptococcus pneumoniae can induce local and systemic diseases such as meningitis, otitis media, and pneumonia. One third of these meningitis cases can be associated with irreversible sensorineural hearing loss whose mechanisms likely involves the exotoxin pneumolysin (PLY) that irreversibly damages cochlear hair cells (HCs). In the respiratory system and in neuron it has been demonstrated that zinc deficiency increases severity and mortality of such infections in animal models and in children. Moreover, zinc supplementation can decrease the severity of pneumococcal respiratory infections. The aim of our study was to assess the potential protective effect of zinc against PLY toxicity on HCs in culture. Our results showed that in the presence of zinc at concentration as low as 1 microM, the toxicity of PLY was largely reduced by about 50% for both inner and outer HCs. At 300 microM of zinc, protection significantly increased with 62 and 55.2% for IHCs and OHCs, respectively. Our results suggest that the protective effect of zinc is likely due to an inhibition of the toxin incorporation and aggregation into the plasma membrane, thus preventing calcium influx through the toxin pores. Our findings raise the possibility that treatments with zinc may help to prevent debilitating otological sequelae from pneumococcal infection.
Franco-Vidal
Valérie
V
Otolaryngology and Skull Base Surgery Department, University of Bordeaux 2 Victor Segalen, Bordeaux, France. valerie.vidal@chu-bordeaux.fr
Beurg
Maryline
M
Darrouzet
Vincent
V
Bébéar
Jean-Pierre
JP
Skinner
Liam J
LJ
Dulon
Didier
D
D000818:Animals; D001426:Bacterial Proteins / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006198:Hair Cells, Auditory / Q000187:drug effects* / Q000473:pathology*; D034381:Hearing Loss / Q000382:microbiology / Q000517:prevention & control; D009924:Organ Culture Techniques; D011008:Pneumococcal Infections / Q000150:complications; D051381:Rats; D017208:Rats, Wistar; D013296:Streptococcus pneumoniae; D013301:Streptolysins / Q000633:toxicity*; D014131:Trace Elements / Q000494:pharmacology*; D015032:Zinc / Q000494:pharmacology*
D001426:Bacterial Proteins; D013301:Streptolysins; D014131:Trace Elements; C032290:plY protein, Streptococcus pneumoniae; D015032:Zinc