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Journal of Bacteriology, August 2005, p. 5376-5386, Vol. 187, No. 15
0021-9193/05/$08.00+0     doi:10.1128/JB.187.15.5376-5386.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

NanA, a Neuraminidase from Streptococcus pneumoniae, Shows High Levels of Sequence Diversity, at Least in Part through Recombination with Streptococcus oralis

Samantha J. King,* Adrian M. Whatmore,{dagger} and Christopher G. Dowson

Infectious Disease Research Group, Department of Biological Sciences, University of Warwick, Coventry CV4 7AL, United Kingdom

Received 1 September 2004/ Accepted 28 April 2005

Streptococcus pneumoniae, an important human pathogen, contains at least two genes, nanA and nanB, that express sialidase activity. NanA is a virulence determinant of pneumococci which is important in animal models of colonization and middle ear infections. The gene encoding NanA was detected in all 106 pneumococcal strains screened that represented 59 restriction profiles. Sequencing confirmed a high level of diversity, up to 17.2% at the nucleotide level and 14.8% at the amino acid level. NanA diversity is due to a number of mechanisms including insertions, point mutations, and recombination generating mosaic genes. The level of nucleotide divergence for each recombinant block is greater than 30% and much higher than the 20% identified within mosaic pbp genes, suggesting that a high selective pressure exists for these alterations. These data indicate that at least one of the four recombinant blocks identified originated from a Streptococcus oralis isolate, demonstrating for the first time that protein virulence determinants of pneumococci have, as identified previously for genes encoding penicillin binding proteins, evolved by recombination with oral streptococci. No amino acid alterations were identified within the aspartic boxes or predicted active site, suggesting that sequence variation may be important in evading the adaptive immune response. Furthermore, this suggests that nanA is an important target of the immune system in the interaction between the pneumococcus and host.


* Corresponding author. Present address: 401A Johnson Pavilion, Department of Microbiology, University of Pennsylvania, Philadelphia, PA 19104-6076. Phone: (215) 573-3510. Fax: (215) 573-4856. E-mail: sking2{at}mail.med.upenn.edu.

{dagger} Present address: Department of Statutory and Exotic Bacterial Diseases, Veterinary Laboratories Agency, Addlestone, Surrey, United Kingdom KT15 3NB.


Journal of Bacteriology, August 2005, p. 5376-5386, Vol. 187, No. 15
0021-9193/05/$08.00+0     doi:10.1128/JB.187.15.5376-5386.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.




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