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Rapid selection of complement-inhibiting protein variants in group A Streptococcus epidemic waves

Nature Medicine volume 5, pages 924–929 (1999)Cite this article

Abstract

Serotype M1 group A Streptococcus strains cause epidemic waves of human infections long thought to be mono- or pauciclonal. The gene encoding an extracellular group A Streptococcus protein (streptococcal inhibitor of complement) that inhibits human complement was sequenced in 1,132 M1 strains recovered from population-based surveillance of infections in Canada, Finland and the United States. Epidemic waves are composed of strains expressing a remarkably heterogeneous array of variants of streptococcal inhibitor of complement that arise very rapidly by natural selection on mucosal surfaces. Thus, our results enhance the understanding of pathogen population dynamics in epidemic waves and infectious disease reemergence.

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Figure 1: Frequency distribution of abundant Sic variants over time in four study localities.
Figure 2: a, Evolutionary tree for sic alleles in a representative local area.
Figure 3: Inhibition of complement-mediated target cell lysis by Sic variants.
Figure 4: Sic variants identified among associated isolates.

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Acknowledgements

We thank W.A. Keitel and J. Dale for critical reading of the manuscript, R.S. Orkiszewski for the mass spectroscopy analysis, I. Eckstrand for support, and S. Ruusunen, R. Scotford and E. Siren for technical assistance. We thank A. Muotiala, H. Seppala, P. Huovinen and the Finnish Study Group for Antimicrobial Resistance for their work and support during collection of the Finnish strains. Specimens from the United States were provided by the Emerging Infections Program Network/Active Bacterial Core Surveillance, supported by a cooperative agreement between the Centers for Disease Control and Prevention and the State Health Departments of California, Connecticut, Georgia, and Minnesota. This study was supported by United States Public Health Service Grants AI-33119 to J.M.M. and GM-50428 to Y.-X. F., and the Canadian Bacterial Disease Network.

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  1. James M. Musser

    Present address: Office of the Chief, Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 903 South 4th Street, Hamilton, Montana, 59840, USA

Authors and Affiliations

  1. Institute for the Study of Human Bacterial Pathogenesis Department of Pathology, Baylor College of Medicine, One Baylor Plaza, Houston, 77030, Texas, USA

    Nancy P. Hoe, Kazumitsu Nakashima, Slawomir Lukomski, Diana Grigsby, Mengyao Liu, Parichher Kordari, Shu-Jun Dou, Xi Pan & James M. Musser

  2. Department of Bacteriology, National Public Health Institute, Mannerheimintie 166, Helsinki, FIN-00300, Finland

    Jaana Vuopio-Varkila & Saara Salmenlinna

  3. Department of Microbiology, Mount Sinai Hospital, 600 University Avenue

    Allison McGeer & Donald E. Low

  4. University of Toronto, M5G 1X5, Ontario, Canada

    Allison McGeer & Donald E. Low

  5. Centers for Disease Control and Prevention, 1600 Clifton Road, NE, Atlanta, 30333, Georgia, USA

    Benjamin Schwartz & Anne Schuchat

  6. eGenomics, New York, 10013, New York, USA

    Steven Naidich

  7. Human Genetics Center, The University of Texas Health Sciences Center, Houston, Texas, 77030, USA

    David De Lorenzo & Yun-Xin Fu

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Correspondence to James M. Musser.

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Hoe, N., Nakashima, K., Lukomski, S. et al. Rapid selection of complement-inhibiting protein variants in group A Streptococcus epidemic waves. Nat Med 5, 924–929 (1999). https://doi.org/10.1038/11369

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