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Infection and Immunity, March 2004, p. 1587-1593, Vol. 72, No. 3
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.3.1587-1593.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

A Locus Contained within a Variable Region of Pneumococcal Pathogenicity Island 1 Contributes to Virulence in Mice

Jeremy S. Brown,1* Sarah M. Gilliland,2 Brian G. Spratt,3 and David W. Holden2

Centre for Respiratory Research, Department of Medicine, Rayne Institute, Royal Free and University College Medical School, London WC1E 6JJ,1 Centre for Molecular Microbiology and Infection, Department of Infectious Diseases, Faculty of Medicine, Imperial College London, London SW7 2AZ,2 Department of Infectious Disease Epidemiology, Faculty of Medicine, St. Mary's Hospital, Imperial College London, London W2 1PG, United Kingdom3

Received 29 October 2003/ Accepted 11 December 2003

We have previously described a 27-kb pathogenicity island of Streptococcus pneumoniae, termed pneumococcal pathogenicity island 1 (PPI1), which contains iron uptake locus piaABCD, required for full virulence in mice, and a further 28 previously uncharacterized genes. We have investigated one of these, Sp1051, which encodes a protein of unknown function. Disruption of Sp1051 does not affect growth in laboratory broth, serum, or blood but impairs virulence in mouse models of infection. When S. pneumoniae capsular serotypes were analyzed by PCR and Southern hybridization, it was found that 33% did not contain Sp1051. Analysis of other genes within PPI1 demonstrated that, compared to the serotype 4 genome published by The Institute for Genome Research (TIGR), the genomes of many strains contain deletions of a variable number of genes between Sp1046 and Sp1064, conforming to one of six different patterns. Amplification by PCR of this PPI1 variable region from a capsular serotype 17 strain and comparison of the sequence to TIGR serotype 4 strain sequence showed that Sp1051 is contained within an 11.3-kb segment of DNA flanked by 7-bp direct repeats within the serotype 4 strain which is not present in the serotype 17 strain. Further comparison of the sequences of this region between the three published S. pneumoniae genomes demonstrated that serotype 19F and strain R6 contain novel complements of genes not present in the serotype 4 strain. These data indicate that there is striking variation in gene content and structure of the 3' region of PPI1 among strains and that this region includes at least one virulence determinant. Gene variation within horizontally acquired DNA such as that of PPI1 may be one factor modulating differences in virulence among strains.

* Corresponding author. Mailing address: Centre for Respiratory Research, Department of Medicine, Royal Free and University College Medical School, Rayne Institute, 5 University St., London WC1E 6JJ, United Kingdom. Phone: (44) (20) 7679 6008. Fax: (44) (20) 7679 6973. E-mail: jeremy.brown{at}ucl.ac.uk.

Editor: J. N. Weiser

Infection and Immunity, March 2004, p. 1587-1593, Vol. 72, No. 3
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.3.1587-1593.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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