Abstract
Chromosomal diversity and relationships among 126 Streptococcus pyogenes strains expressing M1 protein from 13 countries on five continents were analyzed by multilocus enzyme electrophoresis and restriction fragment profiling by pulsed-field gel electrophoresis. All isolates were studied for the presence of the gene encoding streptococcal pyrogenic exotoxin A by PCR. Strain subsets were also examined by automated DNA sequencing for allelic polymorphism in genes encoding M protein (emm), streptococcal pyrogenic exotoxin A (speA), streptokinase (ska), pyrogenic exotoxin B (interleukin-1 beta convertase) (speB), and C5a peptidase (scp). Seven distinct emm1 alleles that encode M proteins differing at one or more amino acids in the N-terminal variable region were identified. Although substantial levels of genetic diversity exist among M1-expressing organisms, most invasive disease episodes are caused by two subclones marked by distinctive multilocus enzyme electrophoretic profiles and pulsed-field gel electrophoresis restriction fragment length polymorphism (RFLP) types. One of these subclones (ET 1/RFLP pattern 1a) has the speA gene and was recovered worldwide. Identity of speA, emm1, speB, and ska alleles in virtually all isolates of ET 1/RFLP type 1a means that these organisms share a common ancestor and that global dispersion of this M1-expressing subclone has occurred very recently. The occurrence of the same emm and ska alleles in strains that are well differentiated in overall chromosomal character demonstrates that horizontal transfer and recombination play a fundamental role in diversifying natural populations of S. pyogenes.
Full Text
The Full Text of this article is available as a PDF (342.9 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Bessen D. E., Hollingshead S. K. Allelic polymorphism of emm loci provides evidence for horizontal gene spread in group A streptococci. Proc Natl Acad Sci U S A. 1994 Apr 12;91(8):3280–3284. doi: 10.1073/pnas.91.8.3280. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bessen D., Fischetti V. A. Influence of intranasal immunization with synthetic peptides corresponding to conserved epitopes of M protein on mucosal colonization by group A streptococci. Infect Immun. 1988 Oct;56(10):2666–2672. doi: 10.1128/iai.56.10.2666-2672.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bisno A. L. Group A streptococcal infections and acute rheumatic fever. N Engl J Med. 1991 Sep 12;325(11):783–793. doi: 10.1056/NEJM199109123251106. [DOI] [PubMed] [Google Scholar]
- Chen C. C., Cleary P. P. Complete nucleotide sequence of the streptococcal C5a peptidase gene of Streptococcus pyogenes. J Biol Chem. 1990 Feb 25;265(6):3161–3167. [PubMed] [Google Scholar]
- Dowson C. G., Hutchison A., Woodford N., Johnson A. P., George R. C., Spratt B. G. Penicillin-resistant viridans streptococci have obtained altered penicillin-binding protein genes from penicillin-resistant strains of Streptococcus pneumoniae. Proc Natl Acad Sci U S A. 1990 Aug;87(15):5858–5862. doi: 10.1073/pnas.87.15.5858. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Duim B., van Alphen L., Eijk P., Jansen H. M., Dankert J. Antigenic drift of non-encapsulated Haemophilus influenzae major outer membrane protein P2 in patients with chronic bronchitis is caused by point mutations. Mol Microbiol. 1994 Mar;11(6):1181–1189. doi: 10.1111/j.1365-2958.1994.tb00394.x. [DOI] [PubMed] [Google Scholar]
- Ehata T., Omata M., Chuang W. L., Yokosuka O., Ito Y., Hosoda K., Ohto M. Mutations in core nucleotide sequence of hepatitis B virus correlate with fulminant and severe hepatitis. J Clin Invest. 1993 Mar;91(3):1206–1213. doi: 10.1172/JCI116281. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Feavers I. M., Heath A. B., Bygraves J. A., Maiden M. C. Role of horizontal genetic exchange in the antigenic variation of the class 1 outer membrane protein of Neisseria meningitidis. Mol Microbiol. 1992 Feb;6(4):489–495. doi: 10.1111/j.1365-2958.1992.tb01493.x. [DOI] [PubMed] [Google Scholar]
- Fischetti V. A., Hodges W. M., Hruby D. E. Protection against streptococcal pharyngeal colonization with a vaccinia: M protein recombinant. Science. 1989 Jun 23;244(4911):1487–1490. doi: 10.1126/science.2660266. [DOI] [PubMed] [Google Scholar]
- Fischetti V. A. Streptococcal M protein: molecular design and biological behavior. Clin Microbiol Rev. 1989 Jul;2(3):285–314. doi: 10.1128/cmr.2.3.285. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Harbaugh M. P., Podbielski A., Hügl S., Cleary P. P. Nucleotide substitutions and small-scale insertion produce size and antigenic variation in group A streptococcal M1 protein. Mol Microbiol. 1993 May;8(5):981–991. doi: 10.1111/j.1365-2958.1993.tb01642.x. [DOI] [PubMed] [Google Scholar]
- Hauser A. R., Stevens D. L., Kaplan E. L., Schlievert P. M. Molecular analysis of pyrogenic exotoxins from Streptococcus pyogenes isolates associated with toxic shock-like syndrome. J Clin Microbiol. 1991 Aug;29(8):1562–1567. doi: 10.1128/jcm.29.8.1562-1567.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Johnson L. P., Schlievert P. M. Group A streptococcal phage T12 carries the structural gene for pyrogenic exotoxin type A. Mol Gen Genet. 1984;194(1-2):52–56. doi: 10.1007/BF00383496. [DOI] [PubMed] [Google Scholar]
- Kapur V., Maffei J. T., Greer R. S., Li L. L., Adams G. J., Musser J. M. Vaccination with streptococcal extracellular cysteine protease (interleukin-1 beta convertase) protects mice against challenge with heterologous group A streptococci. Microb Pathog. 1994 Jun;16(6):443–450. doi: 10.1006/mpat.1994.1044. [DOI] [PubMed] [Google Scholar]
- Kapur V., Majesky M. W., Li L. L., Black R. A., Musser J. M. Cleavage of interleukin 1 beta (IL-1 beta) precursor to produce active IL-1 beta by a conserved extracellular cysteine protease from Streptococcus pyogenes. Proc Natl Acad Sci U S A. 1993 Aug 15;90(16):7676–7680. doi: 10.1073/pnas.90.16.7676. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kapur V., Nelson K., Schlievert P. M., Selander R. K., Musser J. M. Molecular population genetic evidence of horizontal spread of two alleles of the pyrogenic exotoxin C gene (speC) among pathogenic clones of Streptococcus pyogenes. Infect Immun. 1992 Sep;60(9):3513–3517. doi: 10.1128/iai.60.9.3513-3517.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kapur V., Topouzis S., Majesky M. W., Li L. L., Hamrick M. R., Hamill R. J., Patti J. M., Musser J. M. A conserved Streptococcus pyogenes extracellular cysteine protease cleaves human fibronectin and degrades vitronectin. Microb Pathog. 1993 Nov;15(5):327–346. doi: 10.1006/mpat.1993.1083. [DOI] [PubMed] [Google Scholar]
- Kawaoka Y., Webster R. G. Molecular mechanism of acquisition of virulence in influenza virus in nature. Microb Pathog. 1988 Nov;5(5):311–318. doi: 10.1016/0882-4010(88)90032-0. [DOI] [PubMed] [Google Scholar]
- Kholy A. E., Guirguis N. I., Wannamaker L. W., Krause R. M. Newly recognized distinctive M protein associated with certain M type 1 group A streptococci. Infect Immun. 1975 Mar;11(3):551–555. doi: 10.1128/iai.11.3.551-555.1975. [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]
- LANCEFIELD R. C. Current knowledge of type-specific M antigens of group A streptococci. J Immunol. 1962 Sep;89:307–313. [PubMed] [Google Scholar]
- Levinson G., Gutman G. A. Slipped-strand mispairing: a major mechanism for DNA sequence evolution. Mol Biol Evol. 1987 May;4(3):203–221. doi: 10.1093/oxfordjournals.molbev.a040442. [DOI] [PubMed] [Google Scholar]
- Li J., Nelson K., McWhorter A. C., Whittam T. S., Selander R. K. Recombinational basis of serovar diversity in Salmonella enterica. Proc Natl Acad Sci U S A. 1994 Mar 29;91(7):2552–2556. doi: 10.1073/pnas.91.7.2552. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Liang T. J., Hasegawa K., Rimon N., Wands J. R., Ben-Porath E. A hepatitis B virus mutant associated with an epidemic of fulminant hepatitis. N Engl J Med. 1991 Jun 13;324(24):1705–1709. doi: 10.1056/NEJM199106133242405. [DOI] [PubMed] [Google Scholar]
- Martin D. R., Meekin G. E., Finch L. A. Streptococci--are they different in New Zealand? N Z Med J. 1983 Apr 27;96(730):298–301. [PubMed] [Google Scholar]
- Martin D. R., Single L. A. Molecular epidemiology of group A streptococcus M type 1 infections. J Infect Dis. 1993 May;167(5):1112–1117. doi: 10.1093/infdis/167.5.1112. [DOI] [PubMed] [Google Scholar]
- McGuinness B. T., Clarke I. N., Lambden P. R., Barlow A. K., Poolman J. T., Jones D. M., Heckels J. E. Point mutation in meningococcal por A gene associated with increased endemic disease. Lancet. 1991 Mar 2;337(8740):514–517. doi: 10.1016/0140-6736(91)91297-8. [DOI] [PubMed] [Google Scholar]
- McGuinness B. T., Lambden P. R., Heckels J. E. Class 1 outer membrane protein of Neisseria meningitidis: epitope analysis of the antigenic diversity between strains, implications for subtype definition and molecular epidemiology. Mol Microbiol. 1993 Feb;7(4):505–514. doi: 10.1111/j.1365-2958.1993.tb01141.x. [DOI] [PubMed] [Google Scholar]
- Musser J. M., Gray B. M., Schlievert P. M., Pichichero M. E. Streptococcus pyogenes pharyngitis: characterization of strains by multilocus enzyme genotype, M and T protein serotype, and pyrogenic exotoxin gene probing. J Clin Microbiol. 1992 Mar;30(3):600–603. doi: 10.1128/jcm.30.3.600-603.1992. [DOI] [PMC free article] [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]
- Musser J. M., Kapur V., Kanjilal S., Shah U., Musher D. M., Barg N. L., Johnston K. H., Schlievert P. M., Henrichsen J., Gerlach D. Geographic and temporal distribution and molecular characterization of two highly pathogenic clones of Streptococcus pyogenes expressing allelic variants of pyrogenic exotoxin A (Scarlet fever toxin). J Infect Dis. 1993 Feb;167(2):337–346. doi: 10.1093/infdis/167.2.337. [DOI] [PubMed] [Google Scholar]
- Musser J. M., Kapur V., Peters J. E., Hendrix C. W., Drehner D., Gackstetter G. D., Skalka D. R., Fort P. L., Maffei J. T., Li L. L. Real-time molecular epidemiologic analysis of an outbreak of Streptococcus pyogenes invasive disease in US Air Force trainees. Arch Pathol Lab Med. 1994 Feb;118(2):128–133. [PubMed] [Google Scholar]
- Mylvaganam H., Bjorvatn B., Hofstad T., Hjetland R., Hoiby E. A., Holm S. E. Small-fragment restriction endonuclease analysis in epidemiological mapping of group A streptococci. J Med Microbiol. 1994 Apr;40(4):256–260. doi: 10.1099/00222615-40-4-256. [DOI] [PubMed] [Google Scholar]
- Nelson K., Schlievert P. M., Selander R. K., Musser J. M. Characterization and clonal distribution of four alleles of the speA gene encoding pyrogenic exotoxin A (scarlet fever toxin) in Streptococcus pyogenes. J Exp Med. 1991 Nov 1;174(5):1271–1274. doi: 10.1084/jem.174.5.1271. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Norgren M., Norrby A., Holm S. E. Genetic diversity in T1M1 group A streptococci in relation to clinical outcome of infection. J Infect Dis. 1992 Nov;166(5):1014–1020. doi: 10.1093/infdis/166.5.1014. [DOI] [PubMed] [Google Scholar]
- Ohkuni H., Todome Y., Suzuki H., Mizuse M., Kotani N., Horiuchi K., Shikama N., Tsugita A., Johnston K. H. Immunochemical studies and complete amino acid sequence of the streptokinase from Streptococcus pyogenes (group A) M type 12 strain A374. Infect Immun. 1992 Jan;60(1):278–283. doi: 10.1128/iai.60.1.278-283.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Potter E. V., Svartman M., Burt E. G., Finklea J. F., Poon-King T., Earle D. P. Relationship of acute rheumatic fever to acute glomerulonephritis in Trinidad. J Infect Dis. 1972 Jun;125(6):619–625. doi: 10.1093/infdis/125.6.619. [DOI] [PubMed] [Google Scholar]
- Reeves P. Evolution of Salmonella O antigen variation by interspecific gene transfer on a large scale. Trends Genet. 1993 Jan;9(1):17–22. doi: 10.1016/0168-9525(93)90067-R. [DOI] [PubMed] [Google Scholar]
- Schwartz B., Facklam R. R., Breiman R. F. Changing epidemiology of group A streptococcal infection in the USA. Lancet. 1990 Nov 10;336(8724):1167–1171. doi: 10.1016/0140-6736(90)92777-f. [DOI] [PubMed] [Google Scholar]
- Selander R. K., Caugant D. A., Ochman H., Musser J. M., Gilmour M. N., Whittam T. S. Methods of multilocus enzyme electrophoresis for bacterial population genetics and systematics. Appl Environ Microbiol. 1986 May;51(5):873–884. doi: 10.1128/aem.51.5.873-884.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Seppälä H., Vuopio-Varkila J., Osterblad M., Jahkola M., Rummukainen M., Holm S. E., Huovinen P. Evaluation of methods for epidemiologic typing of group A streptococci. J Infect Dis. 1994 Mar;169(3):519–525. doi: 10.1093/infdis/169.3.519. [DOI] [PubMed] [Google Scholar]
- Single L. A., Martin D. R. Clonal differences within M-types of the group A Streptococcus revealed by pulsed field gel electrophoresis. FEMS Microbiol Lett. 1992 Feb 1;70(1):85–89. doi: 10.1016/0378-1097(92)90567-8. [DOI] [PubMed] [Google Scholar]
- Spratt B. G., Bowler L. D., Zhang Q. Y., Zhou J., Smith J. M. Role of interspecies transfer of chromosomal genes in the evolution of penicillin resistance in pathogenic and commensal Neisseria species. J Mol Evol. 1992 Feb;34(2):115–125. doi: 10.1007/BF00182388. [DOI] [PubMed] [Google Scholar]
- Stevens D. L. Invasive group A streptococcus infections. Clin Infect Dis. 1992 Jan;14(1):2–11. doi: 10.1093/clinids/14.1.2. [DOI] [PubMed] [Google Scholar]
- Talkington D. F., Schwartz B., Black C. M., Todd J. K., Elliott J., Breiman R. F., Facklam R. R. Association of phenotypic and genotypic characteristics of invasive Streptococcus pyogenes isolates with clinical components of streptococcal toxic shock syndrome. Infect Immun. 1993 Aug;61(8):3369–3374. doi: 10.1128/iai.61.8.3369-3374.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tucker P. C., Strauss E. G., Kuhn R. J., Strauss J. H., Griffin D. E. Viral determinants of age-dependent virulence of Sindbis virus for mice. J Virol. 1993 Aug;67(8):4605–4610. doi: 10.1128/jvi.67.8.4605-4610.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Whatmore A. M., Kapur V., Sullivan D. J., Musser J. M., Kehoe M. A. Non-congruent relationships between variation in emm gene sequences and the population genetic structure of group A streptococci. Mol Microbiol. 1994 Nov;14(4):619–631. doi: 10.1111/j.1365-2958.1994.tb01301.x. [DOI] [PubMed] [Google Scholar]
- Whatmore A. M., Kehoe M. A. Horizontal gene transfer in the evolution of group A streptococcal emm-like genes: gene mosaics and variation in Vir regulons. Mol Microbiol. 1994 Jan;11(2):363–374. doi: 10.1111/j.1365-2958.1994.tb00316.x. [DOI] [PubMed] [Google Scholar]