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Identification of a Secreted Cholesterol-Dependent Cytolysin (Mitilysin) from Streptococcus mitis

Johanna Jefferies,^1, Leena Nieminen,¹ Lea-Ann Kirkham,¹ Calum Johnston,¹ Andrew Smith,² and Tim J. Mitchell^1*

Division of Infection and Immunity, Glasgow Biomedical Research Centre, Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow G12 8TA,¹ Infection Research Group, Level 9, Glasgow Dental Hospital, 378 Sauchiehall Street, Glasgow G2 3JZ, Scotland, United Kingdom²

Received 24 July 2006/ Accepted 16 October 2006

We have detected a cholesterol-dependent cytolysin, which we have named mitilysin, in a small number of Streptococcus mitis isolates. We have sequenced the mitilysin gene from seven isolates of S. mitis. Comparisons with the pneumococcal pneumolysin gene show 15 amino acid substitutions. S. mitis appear to release mitilysin extracellularly. Certain alleles of mitilysin are not recognized by a monoclonal antibody raised to the related toxin pneumolysin. Based on enzyme-linked immunosorbent assay and neutralization assay results, one isolate of S. mitis may produce a further hemolytic toxin in addition to mitilysin. As genetic exchange is known to occur between S. mitis and Streptococcus pneumoniae, this finding may have implications for the development of vaccines or therapies for pneumococcal disease that are based on pneumolysin.

Published ahead of print on 27 October 2006.

Present address: Scottish Meningococcus and Pneumococcus Reference Laboratory, House on the Hill, Stobhill Hospital, Balornock Rd., Glasgow G21 3UW, Scotland, United Kingdom.