This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Fitzgerald, J. R.
Right arrow Articles by Musser, J. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Fitzgerald, J. R.
Right arrow Articles by Musser, J. M.

 Previous Article  |  Next Article 

Infection and Immunity, May 2003, p. 2827-2838, Vol. 71, No. 5
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.5.2827-2838.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Genome Diversification in Staphylococcus aureus: Molecular Evolution of a Highly Variable Chromosomal Region Encoding the Staphylococcal Exotoxin-Like Family of Proteins

J. Ross Fitzgerald,1,{dagger} Sean D. Reid,1 Eeva Ruotsalainen,2 Timothy J. Tripp,3 MengYao Liu,1 Robert Cole,1 Pentti Kuusela,4 Patrick M. Schlievert,3 Asko Järvinen,2 and James M. Musser1*

Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana 59840,1 Department of Medicine, Division of Infectious Diseases,2 Division of Clinical Microbiology, HUCH Laboratory Diagnostics, Helsinki University Central Hospital, Finland,4 Department of Microbiology, University of Minnesota Medical School, Minneapolis, Minnesota 554553

Received 20 November 2002/ Returned for modification 14 January 2003/ Accepted 12 February 2003

Recent genomic studies have revealed extensive variation in natural populations of many pathogenic bacteria. However, the evolutionary processes which contribute to much of this variation remain unclear. A previous whole-genome DNA microarray study identified variation at a large chromosomal region (RD13) of Staphylococcus aureus which encodes a family of proteins with homology to staphylococcal and streptococcal superantigens, designated staphylococcal exotoxin-like (SET) proteins. In the present study, RD13 was found in all 63 S. aureus isolates of divergent clonal, geographic, and disease origins but contained a high level of variation in gene content in different strains. A central variable region which contained from 6 to 10 different set genes, depending on the strain, was identified, and DNA sequence analysis suggests that horizontal gene transfer and recombination have contributed to the diversification of RD13. Phylogenetic analysis based on the RD13 DNA sequence of 18 strains suggested that loss of various set genes has occurred independently several times, in separate lineages of pathogenic S. aureus, providing a model to explain the molecular variation of RD13 in extant strains. In spite of multiple episodes of set deletion, analysis of the ratio of silent substitutions in set genes to amino acid replacements in their products suggests that purifying selection (selective constraint) is acting to maintain SET function. Further, concurrent transcription in vitro of six of the seven set genes in strain COL was detected, indicating that the expression of set genes has been maintained in contemporary strains, and Western immunoblot analysis indicated that multiple SET proteins are expressed during the course of human infections. Overall, we have shown that the chromosomal region RD13 has diversified extensively through episodes of gene deletion and recombination. The coexpression of many set genes and the production of multiple SET proteins during human infection suggests an important role in host-pathogen interactions.

* Corresponding author. Mailing address: Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 903 South 4th St., Hamilton, MT 59840. Phone: (406) 363-9315. Fax: (406) 363-9427. E-mail: jmusser{at}niaid.nih.gov.

Editor: D. L. Burns

{dagger} Present address: Department of Microbiology, Moyne Institute of Preventive Medicine, University of Dublin, Trinity College, Dublin 2, Ireland.

Infection and Immunity, May 2003, p. 2827-2838, Vol. 71, No. 5
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.5.2827-2838.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Paauw, A., Caspers, M. P. M., Leverstein-van Hall, M. A., Schuren, F. H. J., Montijn, R. C., Verhoef, J., Fluit, A. C. (2009). Identification of resistance and virulence factors in an epidemic Enterobacter hormaechei outbreak strain. Microbiology 155: 1478-1488 [Abstract] [Full Text]  
  • Dordet-Frisoni, E., Dorchies, G., De Araujo, C., Talon, R., Leroy, S. (2007). Genomic Diversity in Staphylococcus xylosus. Appl. Environ. Microbiol. 73: 7199-7209 [Abstract] [Full Text]  
  • Jongerius, I., Kohl, J., Pandey, M. K., Ruyken, M., van Kessel, K. P.M., van Strijp, J. A.G., Rooijakkers, S. H.M. (2007). Staphylococcal complement evasion by various convertase-blocking molecules. JEM 204: 2461-2471 [Abstract] [Full Text]  
  • Ramsland, P. A., Willoughby, N., Trist, H. M., Farrugia, W., Hogarth, P. M., Fraser, J. D., Wines, B. D. (2007). Structural basis for evasion of IgA immunity by Staphylococcus aureus revealed in the complex of SSL7 with Fc of human IgA1. Proc. Natl. Acad. Sci. USA 104: 15051-15056 [Abstract] [Full Text]  
  • Abi-Rached, L., Dorighi, K., Norman, P. J., Yawata, M., Parham, P. (2007). Episodes of Natural Selection Shaped the Interactions of IgA-Fc with Fc{alpha}RI and Bacterial Decoy Proteins. J. Immunol. 178: 7943-7954 [Abstract] [Full Text]  
  • Bestebroer, J., Poppelier, M. J. J. G., Ulfman, L. H., Lenting, P. J., Denis, C. V., van Kessel, K. P. M., van Strijp, J. A. G., de Haas, C. J. C. (2007). Staphylococcal superantigen-like 5 binds PSGL-1 and inhibits P-selectin-mediated neutrophil rolling. Blood 109: 2936-2943 [Abstract] [Full Text]  
  • Smyth, D. S., Meaney, W. J., Hartigan, P. J., Smyth, C. J. (2007). Occurrence of ssl genes in isolates of Staphylococcus aureus from animal infection. J Med Microbiol 56: 418-425 [Abstract] [Full Text]  
  • Aguiar-Alves, F., Medeiros, F., Fernandes, O., Gudziki Pereira, R. M., Perdreau-Remington, F., Riley, L. W. (2006). New Staphylococcus aureus Genotyping Method Based on Exotoxin (set) Genes.. J. Clin. Microbiol. 44: 2728-2732 [Abstract] [Full Text]  
  • Tsuru, T., Kawai, M., Mizutani-Ui, Y., Uchiyama, I., Kobayashi, I. (2006). Evolution of Paralogous Genes: Reconstruction of Genome Rearrangements Through Comparison of Multiple Genomes Within Staphylococcus aureus. Mol Biol Evol 23: 1269-1285 [Abstract] [Full Text]  
  • Laughton, J. M., Devillard, E., Heinrichs, D. E., Reid, G., McCormick, J. K. (2006). Inhibition of expression of a staphylococcal superantigen-like protein by a soluble factor from Lactobacillus reuteri.. Microbiology 152: 1155-1167 [Abstract] [Full Text]  
  • Kuhn, G., Francioli, P., Blanc, D. S. (2006). Evidence for Clonal Evolution among Highly Polymorphic Genes in Methicillin-Resistant Staphylococcus aureus. J. Bacteriol. 188: 169-178 [Abstract] [Full Text]  
  • Fraser-Liggett, C. M. (2005). Insights on biology and evolution from microbial genome sequencing. Genome Res 15: 1603-1610 [Abstract] [Full Text]  
  • Molenaar, D., Bringel, F., Schuren, F. H., de Vos, W. M., Siezen, R. J., Kleerebezem, M. (2005). Exploring Lactobacillus plantarum Genome Diversity by Using Microarrays. J. Bacteriol. 187: 6119-6127 [Abstract] [Full Text]  
  • Wright, J. S. III, Traber, K. E., Corrigan, R., Benson, S. A., Musser, J. M., Novick, R. P. (2005). The agr Radiation: an Early Event in the Evolution of Staphylococci. J. Bacteriol. 187: 5585-5594 [Abstract] [Full Text]  
  • Hughes, A. L., Friedman, R. (2005). Nucleotide Substitution and Recombination at Orthologous Loci in Staphylococcus aureus. J. Bacteriol. 187: 2698-2704 [Abstract] [Full Text]  
  • Langley, R., Wines, B., Willoughby, N., Basu, I., Proft, T., Fraser, J. D. (2005). The Staphylococcal Superantigen-Like Protein 7 Binds IgA and Complement C5 and Inhibits IgA-Fc{alpha}RI Binding and Serum Killing of Bacteria. J. Immunol. 174: 2926-2933 [Abstract] [Full Text]  
  • Rigoulay, C., Entenza, J. M., Halpern, D., Widmer, E., Moreillon, P., Poquet, I., Gruss, A. (2005). Comparative Analysis of the Roles of HtrA-Like Surface Proteases in Two Virulent Staphylococcus aureus Strains. Infect. Immun. 73: 563-572 [Abstract] [Full Text]  
  • Saunders, N. A., Underwood, A., Kearns, A. M., Hallas, G. (2004). A virulence-associated gene microarray: a tool for investigation of the evolution and pathogenic potential of Staphylococcus aureus. Microbiology 150: 3763-3771 [Abstract] [Full Text]  
  • Yildirim, S., Lin, W., Hitchins, A. D., Jaykus, L.-A., Altermann, E., Klaenhammer, T. R., Kathariou, S. (2004). Epidemic Clone I-Specific Genetic Markers in Strains of Listeria monocytogenes Serotype 4b from Foods. Appl. Environ. Microbiol. 70: 4158-4164 [Abstract] [Full Text]  
  • Holtfreter, S., Bauer, K., Thomas, D., Feig, C., Lorenz, V., Roschack, K., Friebe, E., Selleng, K., Lovenich, S., Greve, T., Greinacher, A., Panzig, B., Engelmann, S., Lina, G., Broker, B. M. (2004). egc-Encoded Superantigens from Staphylococcus aureus Are Neutralized by Human Sera Much Less Efficiently than Are Classical Staphylococcal Enterotoxins or Toxic Shock Syndrome Toxin. Infect. Immun. 72: 4061-4071 [Abstract] [Full Text]  
  • Al-Shangiti, A. M., Naylor, C. E., Nair, S. P., Briggs, D. C., Henderson, B., Chain, B. M. (2004). Structural Relationships and Cellular Tropism of Staphylococcal Superantigen-Like Proteins. Infect. Immun. 72: 4261-4270 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»