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Journal of Clinical Microbiology, January 2006, p. 151-159, Vol. 44, No. 1
0095-1137/06/$08.00+0     doi:10.1128/JCM.44.1.151-159.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Identification of Invasive Serotype 1 Pneumococcal Isolates That Express Nonhemolytic Pneumolysin

Lea-Ann S. Kirkham,1,{dagger} Johanna M. C. Jefferies,1,{dagger} Alison R. Kerr,1 Yu Jing,1 Stuart C. Clarke,1,2 Andrew Smith,3 and Tim J. Mitchell1*

Division of Infection and Immunity, Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow G12 8QQ, United Kingdom,1 Scottish Meningococcus and Pneumococcus Reference Laboratory, Stobhill Hospital, Glasgow G21 3UW, United Kingdom,2 Infection Research Group, Level 9, Glasgow Dental School, University of Glasgow, Glasgow G2 3JZ, United Kingdom3

Received 10 August 2005/ Returned for modification 19 September 2005/ Accepted 31 October 2005

Recently, there has been an increase in invasive pneumococcal disease (IPD) caused by serotype 1 Streptococcus pneumoniae throughout Europe. Serotype 1 IPD is associated with bacteremia and pneumonia in Europe and North America, especially in neonates, and is ranked among the top five most prevalent pneumococcal serotypes in at least 10 countries. The currently licensed pediatric pneumococcal vaccine does not afford protection to this serotype. Upon screening of 252 clinical isolates of S. pneumoniae, we discovered mutations in the pneumolysin gene of two out of the four serotype 1 strains present in the study group. Analysis of an additional 28 serotype 1 isolates from patients with IPD from various Scottish Health Boards, revealed that >50% had mutations in their pneumolysin genes. This resulted in the expression of nonhemolytic forms of pneumolysin. All of the strains producing nonhemolytic pneumolysin were sequence type 306 (ST306), whereas those producing "wild-type" pneumolysin were ST227. The mutations were in a region of pneumolysin involved in pore formation. These mutations can be made in vitro to give the nonhemolytic phenotype. Pneumolysin is generally conserved throughout all serotypes of S. pneumoniae and is essential for full invasive disease; however, it appears that serotype 1 ST306 does not require hemolytically active pneumolysin to cause IPD.

* Corresponding author. Mailing address: Division of Infection and Immunity, Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow G12 8QQ, Scotland. Phone: 44 (0) 141 3303740. Fax: 44 (0) 141 3303727. E-mail: t.mitchell{at}bio.gla.ac.uk.

{dagger} L.-A.S.K. and J.M.C.J. contributed equally to this article.

Journal of Clinical Microbiology, January 2006, p. 151-159, Vol. 44, No. 1
0095-1137/06/$08.00+0     doi:10.1128/JCM.44.1.151-159.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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