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Journal of Bacteriology, December 2008, p. 7773-7785, Vol. 190, No. 23
0021-9193/08/$08.00+0     doi:10.1128/JB.00672-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Genome Sequence of a Nephritogenic and Highly Transformable M49 Strain of Streptococcus pyogenes{triangledown} ,{dagger}

W. Michael McShan,1* Joseph J. Ferretti,2 Tadahiro Karasawa,4 Alexander N. Suvorov,5 Shaoping Lin,3 Biafang Qin,3 Honggui Jia,3 Steve Kenton,3 Fares Najar,3 Hongmin Wu,3 Julie Scott,1 Bruce A. Roe,3 and Dragutin J. Savic1

Department of Pharmaceutical Sciences,1 Department of Microbiology and Immunology, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma,2 Department of Chemistry, The University of Oklahoma, Norman, Oklahoma,3 Department of Bacteriology, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan,4 Department of Molecular Microbiology, Institute of Experimental Medicine, St. Petersburg, Russia5

Received 13 May 2008/ Accepted 17 September 2008

The 1,815,783-bp genome of a serotype M49 strain of Streptococcus pyogenes (group A streptococcus [GAS]), strain NZ131, has been determined. This GAS strain (FCT type 3; emm pattern E), originally isolated from a case of acute post-streptococcal glomerulonephritis, is unusually competent for electrotransformation and has been used extensively as a model organism for both basic genetic and pathogenesis investigations. As with the previously sequenced S. pyogenes genomes, three unique prophages are a major source of genetic diversity. Two clustered regularly interspaced short palindromic repeat (CRISPR) regions were present in the genome, providing genetic information on previous prophage encounters. A unique cluster of genes was found in the pathogenicity island-like emm region that included a novel Nudix hydrolase, and, further, this cluster appears to be specific for serotype M49 and M82 strains. Nudix hydrolases eliminate potentially hazardous materials or prevent the unbalanced accumulation of normal metabolites; in bacteria, these enzymes may play a role in host cell invasion. Since M49 S. pyogenes strains have been known to be associated with skin infections, the Nudix hydrolase and its associated genes may have a role in facilitating survival in an environment that is more variable and unpredictable than the uniform warmth and moisture of the throat. The genome of NZ131 continues to shed light upon the evolutionary history of this human pathogen. Apparent horizontal transfer of genetic material has led to the existence of highly variable virulence-associated regions that are marked by multiple rearrangements and genetic diversification while other regions, even those associated with virulence, vary little between genomes. The genome regions that encode surface gene products that will interact with host targets or aid in immune avoidance are the ones that display the most sequence diversity. Thus, while natural selection favors stability in much of the genome, it favors diversity in these regions.


* Corresponding author. Mailing address: Department of Pharmaceutical Sciences, University of Oklahoma Health Sciences Center, P.O. Box 26901, CPB307, Oklahoma City, OK. Phone: (405) 271-6593. Fax: (405) 271-7505. E-mail: William-McShan{at}ouhsc.edu

{triangledown} Published ahead of print on 26 September 2008.

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


Journal of Bacteriology, December 2008, p. 7773-7785, Vol. 190, No. 23
0021-9193/08/$08.00+0     doi:10.1128/JB.00672-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.




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