Abstract
One of the most prevalent genetic lineages of group A streptococci (GAS) harbors a genomic locus termed the large vir regulon, which contains an emm gene encoding the antiphagocytic M protein, and structurally related fcrA and enn (emm-related) genes encoding immunoglobulin-binding proteins. In the present study more than 100 large vir regulons from 42 different GAS serotypes were analyzed by PCR and partial DNA sequencing. On comparing these data to published sequences, sites of mutational and putative recombinational events were identified and ordered with respect to their intra/intergenic or intra/intergenomic nature. The emm-related genes were found to display small intragenic deletions or insertions, were completely deleted from, or newly inserted into the genome, or were fused to adjacent genes. Intergenomic exchanges of complete emm-related genes, or segments thereof, between different vir regulons were detected. Most of these processes seem to involve short flanking direct repeats. Occasionally, the structural changes could be correlated with changes in the functions of the encoded proteins.
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Bessen DE, Fischetti VA (1992) Nucleotide sequences of two adjacent M or M-like protein genes of group A streptococci: different RNA transcript levels and identification of a unique immunoglobulin A-binding protein. Infect Immun 60:124–135
Bessen D, Jones KF, Fischetti VA (1989) Evidence for two distinct classes of streptococcal M protein and their relationship to rheumatic fever. J Exp Med 169:269–283
Boyle MDP, Hawlitzky J, Raeder R, Podbielski A (1994) Analysis of genes encoding two unique type IIa immunoglobulin G-binding proteins expressed by a single group A streptococcal isolate. Infect Immun 62:1336–1347
Caparon MG, Scott JR (1987) Identification of a gene that regulates expression of M protein, the major virulence determinant of group A streptococci. Proc Natl Acad Sci USA 84:8677–8681
Chen CC, Cleary PP (1990) Complete nucleotide sequence of the streptococcal C5a peptidase gene of Streptococcus pyogenes. J Biol Chem 265:3161–3167
Cleary PP, LaPenta D, Heath D, Haanes EJ, Chen C (1991) A virulence regulon in Streptococcus pyogenes. In: Dunny GM, Cleary PP, McKay LL (eds) Genetics and molecular biology of streptococci, lactococci, and enterococci. American Society for Microbiology, Washington DC, pp 147–151
Collis CM, Grammaticopoulos G, Briton J, Stokes HW, Hall RM (1993) Site-specific insertion of gene cassettes into integrons. Mol Microbiol 9:41–52
Dybvig K, Hollingshead SK, Heath DG, Clewell DB, Sun F, Woodard A (1992) Degenerate oligonucleotide primers for enzymatic amplification of recA sequences from gram-positive bacteria and mycoplasmas. J Bacteriol 174:2729–2732
Ehrlich SD (1989) Illegitimate recombination in bacteria. In: Berg D, Howe M (eds) Mobile DNA. American Society for Microbiology, Washington DC, pp 797–829
Fischetti VA (1989) Streptococcal M protein: molecular design and biological behavior. Clin Microbiol Rev 2:285–314
Frithz E, Heden LO, Lindahl G (1989) Extensive sequence homology between IgA receptor and M proteins in Streptococcus pyogenes. Mol Microbiol 3:1111–1119
Gomi H, Hozumi T, Hattori S, Tagawa C, Kishimoto F, Björck L (1990) The gene sequence and some properties of protein H. J Immunol 144:4046–4052
Haanes EJ, Cleary PP (1989) Identification of a divergent M protein gene and an M protein-related gene family in Streptococcus pyogenes serotype 49. J Bacteriol 171:6397–6408
Haanes EJ, Heath DG, Cleary PP (1992) Architecture of the vir regulons of group A streptococci parallel opacity factor phenotype and M protein class. J Bacteriol 174:4967–4976
Haanes-Fritz E, Kraus W, Burdett V, Dale JB, Beachey EH, Cleary P (1988) Comparison of the leader sequences of four group A streptococcal M protein genes. Nucleic Acids Res 16:4667–4677
Harbaugh MP, Podbielski A, Hügl S, Cleary PP (1993) Nucleotide substitutions and small-scale insertion produce size and antigenic variation in group A streptococcal M1 protein. Mol Microbiol 8:981–991
Heath DG, Cleary PP (1989) Fc-receptor and M-protein genes of group A streptococci are products of gene duplication. Proc Natl Acad Sci USA 86:4741–4745
Heden LO, Lindahl G (1993) Conserved and variable regions in protein Arp, the IgA receptor of Streptococcus pyogenes. J Gen Microbiol 139:2067–2074
Hollingshead SK, Fischetti VA, Scott JR (1986) Complete nucleotide sequence of type 6 M protein of the group A streptococcus. J Biol Chem 261:1677–1686
Hollingshead SK, Fischetti VA, Scott JR (1987) Size variation in group A streptococcal M proteins is generated by homologous recombination between intragenic repeats. Mol Gen Genet 207:196–203
Hollingshead SK, Readdy TL, Yung DL, Bessen DE (1993) Structural heterogeneity of the emm gene cluster in group A streptococci. Mol Microbiol 8:707–717
Jeppson H, Frithz E, Heden LO (1992) Duplication of a DNA sequence homologous to genes for immunoglobulin receptors and M proteins in Streptococcus pyogenes. FEMS Microbiol Lett 92:139–146
Kaufhold A, Podbielski A, Johnson DR, Kaplan EL, Lütticken R (1992) M protein gene typing of Streptococcus pyogenes by nonradioactively labeled oligonucleotide probes. J Clin Microbiol 30:2391–2397
Kaufhold A, Podbielski A, Kriz-Kuzemenska P (1993) Identification of M types of group A streptococci. J Clin Microbiol 31:1955–1956
Manjula BN, Khandke KM, Fairwell T, Relf WA, Sriprakash KS (1991) Heptad motifs within the distal subdomain of the coiled-coil rod region of M protein from rheumatic fever- and nephritis-associated serotypes of group A streptococci are distinct from each other: nucleotide sequence of the M57 gene and relation of the deduced amino acid sequence to other M proteins. J Prot Chem 10:1369–384
Martin NJ, Kaplan EL, Gerber MA, Menegus MA, Randolph M, Bell K, Cleary PP (1990) Comparison of epidemic and endemic group G streptococci by restriction enzyme analysis. J Clin Microbiol 28:1881–1886
Miller L, Gray L, Beachey E, Kehoe M (1988) Antigenic variation among group A streptococcal M proteins. J Biol Chem 263:5668–5673
Mouw AR, Beachey EH, Burdett V (1988) Molecular evolution of streptococcal M protein: cloning and nucleotide sequence of the type 24 M protein gene and relation to other genes of Streptococcus pyogenes. J Bacteriol 170:676–684
O'Toole P, Stenberg L, Rissler M, Lindahl G (1992) Two major classes in the M protein family in group A streptococci. Proc Natl Acad Sci USA 89:8661–8665
Otten RA, Boyle MDP (1991) Bacterial immunoglobulin-binding proteins — future trends. In: Boyle MDP (ed) Bacterial immunoglobulin-binding proteins. Academic Press, San Diego, pp 425–452
Perez-Casal J, Caparon MG, Scott JR (1991) Mry, a trans-acting positive regulator of the M protein gene of Streptococcus pyogenes with similarity to the receptor proteins of two-component regulatory systems. J Bacteriol 173:2617–2624
Podbielski A (1992) Ubiquitous occurrence of virR and scpA genes in group A streptococci. Med Microbiol Immunol 181:227–240
Podbielski A (1993) Three different types of organization of the vir regulon in group A streptococci. Mol Gen Genet 237:287–300
Podbielski A, Melzer B, Lütticken R (1991) Application of the polymerase chain reaction to study the M protein(-like) gene family in beta-hemolytic streptococci. Med Microbiol Immunol 180:213–227
Podbielski A, Kaufhold A, Cleary PP (1993) PCR-mediated amplification of group A streptococcal genes encoding immunoglobulin-binding proteins. Immuno Methods 2:55–64
Podbielski A, Weber-Heynemann J, Cleary PP (1994a) Immunoglobulin-binding FcrA and Enn proteins and M proteins of group A streptococci evolved independently from a common ancestral protein. Med Microbiol Immunol 183:33–42
Podbielski A, Hawlitzky J, Pack TD, Flosdorff A, Boyle MDP (1994b) A group A streptococcal Enn protein potentially resulting from intergenomic recombination exhibits atypical immunoglobulinbinding characteristics. Mol Microbiol 13: in press
Raeder R, Faulmann EL, Boyle MDP (1991) Evidence for functional heterogeneity in IgG Fc-binding proteins associated with group A streptococci. J Immunol 146:1247–1253
Robbins JC, Spanier JG, Jones SJ, Simpson WJ, Cleary PP (1987) Streptococcus pyogenes type 12 M protein gene regulation by upstream sequences. J Bacteriol 169:5633–5640
Smith HE, Reek FH, Vecht U, Gielkens ALJ, Smits MA (1993) Repeats in an extracellular protein of weakly pathogenic strains of Streptococcus suis type 2 are absent in pathogenic strains. Infect Immun 61:3318–3326
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Podbielski, A., Krebs, B. & Kaufhold, A. Genetic variability of the emm-related genes of the large vir regulon of group A streptococci: potential intra- and intergenomic recombination events. Molec. Gen. Genet. 243, 691–698 (1994). https://doi.org/10.1007/BF00279579
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DOI: https://doi.org/10.1007/BF00279579