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Journal of Clinical Microbiology, September 2008, p. 3033-3041, Vol. 46, No. 9
0095-1137/08/$08.00+0     doi:10.1128/JCM.00005-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Opa Protein Repertoires of Disease-Causing and Carried Meningococci{triangledown} ,{dagger}

Martin J. Callaghan,1* Caroline Buckee,2 Noel D. McCarthy,3 Ana Belén Ibarz Pavón,3 Keith A. Jolley,3 Saul Faust,4 Stephen J. Gray,5 Edward B. Kaczmarski,5 Michael Levin,6 J. Simon Kroll,6 Martin C. J. Maiden,3 and Andrew J. Pollard1

Dept. of Paediatrics, Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Churchill Hospital, Headington, Oxford OX3 9DU, United Kingdom,1 Dept. of Zoology, University of Oxford, South Parks Road, Oxford OX1 3PS, United Kingdom,2 Peter Medawar Building for Pathogen Research and Dept. of Zoology, University of Oxford, South Parks Rd., Oxford OX1 3SY, United Kingdom,3 Wellcome Trust Clinical Research Facility, University of Southampton School of Medicine, Mailpoint 218, Level C, West Wing, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, United Kingdom,4 Meningococcal Reference Unit, Health Protection Agency, Manchester Royal Infirmary, Oxford Road, Manchester M13 9WZ, United Kingdom,5 Dept. of Paediatrics, Faculty of Medicine, Wright Fleming Institute, Imperial College London, St. Mary's Campus, Norfolk Place, London W2 1PG, United Kingdom6

Received 17 December 2007/ Returned for modification 15 February 2008/ Accepted 21 May 2008

The meningococcal Opa proteins play an important role in pathogenesis by mediating invasion of human cells. The aim of this investigation was to determine whether carried and disease-associated meningococci possess different Opa repertoires and whether the diversity of these proteins is associated with clinical severity of disease. Opa repertoires in 227 disease-associated meningococci, isolated in the United Kingdom over a period of 6 years, were compared to the repertoires in 190 asymptomatically carried meningococci isolated in the United Kingdom from a contemporary, nonepidemic period. Multidimensional scaling (MDS) was employed to investigate the association between Opa repertoires and multilocus sequence typing (MLST) genotypes. Associations with clinical severity were also analyzed statistically. High levels of diversity were observed in opa alleles, variable regions, and repertoires, and MDS revealed that MLST genotypes were strongly associated with particular Opa repertoires. Individual Opa proteins or repertoires were not associated with clinical severity, though there was a trend toward an association with the opaD locus. Meningococcal Opa repertoire is strongly linked to MLST genotype irrespective of epidemiological sampling and therefore correlates with invasiveness. It is not, however, strongly associated with severity of meningococcal disease.

* Corresponding author. Mailing address: Dept. of Paediatrics, Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Churchill Hospital, Headington, Oxford OX3 9DU, United Kingdom. Phone: 44 (0)1865 857 461. Fax: 44 (0)1865 857 420. E-mail: martin.callaghan{at}paediatrics.ox.ac.uk

{triangledown} Published ahead of print on 28 May 2008.

{dagger} Supplemental material for this article may be found at http://jcm.asm.org/.

Journal of Clinical Microbiology, September 2008, p. 3033-3041, Vol. 46, No. 9
0095-1137/08/$08.00+0     doi:10.1128/JCM.00005-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



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