Abstract
Streptococcus pyogenes strains producing pyrogenic exotoxin A (scarlet fever toxin) have recently caused episodes of streptococcal toxic-shock- like syndrome (TSLS). We exploited knowledge of genetic diversity and relationships among exotoxin A-producing patient strains provided by multilocus enzyme electrophoresis to select strains for comparative sequencing of toxin genes. Our analysis identified four alleles of speA in natural populations, one of which (speA1) occurs in many distinct clonal lineages and is probably old. Two other alleles (speA2 and speA3), characterized solely by single amino acid substitutions, were each identified in single clones that together have caused the majority of TSLS episodes. It is unlikely that these alleles have had a long association with S. pyogenes clones. A fourth allele (speA4) also is present in a single phylogenetic lineage and is 9% divergent from the other three toxin alleles. An absence of synonomous (silent) nucleotide changes in speA2 and speA3 is unusual and suggests that the allelic variation is not selectively neutral, which implies that the toxins are not functionally equivalent. These results may be important in helping to understand the recent increase in frequency and severity of disease caused by S. pyogenes.
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- Gaworzewska E., Colman G. Changes in the pattern of infection caused by Streptococcus pyogenes. Epidemiol Infect. 1988 Apr;100(2):257–269. doi: 10.1017/s095026880006739x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Givner L. B., Abramson J. S., Wasilauskas B. Apparent increase in the incidence of invasive group A beta-hemolytic streptococcal disease in children. J Pediatr. 1991 Mar;118(3):341–346. doi: 10.1016/s0022-3476(05)82144-4. [DOI] [PubMed] [Google Scholar]
- Gray E. D., Wannamaker L. W., Ayoub E. M., el Kholy A., Abdin Z. H. Cellular immune responses to extracellular streptococcal products in rheumatic heart disease. J Clin Invest. 1981 Sep;68(3):665–671. doi: 10.1172/JCI110301. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Grossman D., Cook R. G., Sparrow J. T., Mollick J. A., Rich R. R. Dissociation of the stimulatory activities of staphylococcal enterotoxins for T cells and monocytes. J Exp Med. 1990 Dec 1;172(6):1831–1841. doi: 10.1084/jem.172.6.1831. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Köhler W. Streptococcal toxic shock syndrome. Zentralbl Bakteriol. 1990 Mar;272(3):257–264. doi: 10.1016/s0934-8840(11)80026-5. [DOI] [PubMed] [Google Scholar]
- Lee P. K., Schlievert P. M. Quantification and toxicity of group A streptococcal pyrogenic exotoxins in an animal model of toxic shock syndrome-like illness. J Clin Microbiol. 1989 Aug;27(8):1890–1892. doi: 10.1128/jcm.27.8.1890-1892.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Marrack P., Kappler J. The staphylococcal enterotoxins and their relatives. Science. 1990 May 11;248(4956):705–711. doi: 10.1126/science.2185544. [DOI] [PubMed] [Google Scholar]
- Martin P. R., Høiby E. A. Streptococcal serogroup A epidemic in Norway 1987-1988. Scand J Infect Dis. 1990;22(4):421–429. doi: 10.3109/00365549009027073. [DOI] [PubMed] [Google Scholar]
- Musser J. M., Hauser A. R., Kim M. H., Schlievert P. M., Nelson K., Selander R. K. Streptococcus pyogenes causing toxic-shock-like syndrome and other invasive diseases: clonal diversity and pyrogenic exotoxin expression. Proc Natl Acad Sci U S A. 1991 Apr 1;88(7):2668–2672. doi: 10.1073/pnas.88.7.2668. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ochman H., Wilson A. C. Evolution in bacteria: evidence for a universal substitution rate in cellular genomes. J Mol Evol. 1987;26(1-2):74–86. doi: 10.1007/BF02111283. [DOI] [PubMed] [Google Scholar]
- Strömberg A., Romanus V., Burman L. G. Outbreak of group A streptococcal bacteremia in Sweden: an epidemiologic and clinical study. J Infect Dis. 1991 Sep;164(3):595–598. doi: 10.1093/infdis/164.3.595. [DOI] [PubMed] [Google Scholar]
- Weeks C. R., Ferretti J. J. Nucleotide sequence of the type A streptococcal exotoxin (erythrogenic toxin) gene from Streptococcus pyogenes bacteriophage T12. Infect Immun. 1986 Apr;52(1):144–150. doi: 10.1128/iai.52.1.144-150.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yu C. E., Ferretti J. J. Molecular epidemiologic analysis of the type A streptococcal exotoxin (erythrogenic toxin) gene (speA) in clinical Streptococcus pyogenes strains. Infect Immun. 1989 Dec;57(12):3715–3719. doi: 10.1128/iai.57.12.3715-3719.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]