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This Article Full Text Full Text (PDF) All Versions of this Article: 568/1/211    most recent jphysiol.2005.092478v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Beurg, M. Articles by Dulon, D. Search for Related Content PubMed PubMed Citation Articles by Beurg, M. Articles by Dulon, D.

¹ Laboratoire de Biologie Cellulaire et Moléculaire de l'Audition, EA3665, Université Victor Segalen Bordeaux 2, Hôpital Pellegrin, 33076 Bordeaux, France
² Division of Infection and Immunity, University of Glasgow, Glasgow, UK

Streptoccocus pneumoniae infection can result in local and systemic diseases such as otitis media, pneumonia and meningitis. Sensorineural hearing loss associated with this infection is mediated by the release of an exotoxin, pneumolysin. The goal of the present study was to characterize the mechanisms of pneumolysin toxicity in cochlear hair cells in vitro. Pneumolysin induced severe damage in cochlear hair cells, ranging from stereocilia disorganization to total cell loss. Surprisingly, pneumolysin-induced cell death preferentially targeted inner hair cells. Pneumolysin triggered in vitro cell death by an influx of calcium. Extracellular calcium appeared to enter the cell through a pore formed by the toxin. Buffering intracellular calcium with BAPTA improved hair cell survival. The mitochondrial apoptotic pathway involved in pneumolysin-induced cell death was demonstrated by the use of bongkrekic acid. Binding of pneumolysin to the hair cell plasma membrane was required to induce cell death. Increasing external calcium reduced cell toxicity by preventing the binding of pneumolysin to hair cell membranes. These results showed the significant role of calcium both in triggering pneumolysin-induced hair cell apoptosis and in preventing the toxin from binding to its cellular target.

(Received 10 June 2005; accepted after revision 27 July 2005; first published online 28 July 2005)
Corresponding author M. Beurg: EA-3665 Université Victor Segalen Bordeaux 2, Laboratoire de Biologie Cellulaire et Moléculaire de l'Audition, Hôpital Pellegrin, Bat PQR, 33076 Bordeaux, France. Email: maryline.beurg{at}bordeaux.inserm.fr