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M-protein and other intrinsic virulence factors of Streptococcus pyogenes are encoded on an ancient pathogenicity island.

Panchaud A, Guy L, Collyn F, Haenni M, Nakata M, Podbielski A, Moreillon P, Roten CA - BMC Genomics (2009)

Bottom Line: The stability of this SSR, combined to its presence in all sequenced S. pyogenes sequenced genome, suggests that it results from an ancient acquisition.Thus, this non-phagic SSR is compatible with a pathogenicity island, acquired before S. pyogenes speciation.Its potential excision might bear relevance for vaccine development, because vaccines targeting M-protein might select for M-protein-negative variants that still carry other virulence determinants.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Fundamental Microbiology, University of Lausanne, Quartier UNIL-Sorge, Bâtiment Biophore, Lausanne, Switzerland. panchaud@u.washington.edu

ABSTRACT

Background: The increasing number of completely sequenced bacterial genomes allows comparing their architecture and genetic makeup. Such new information highlights the crucial role of lateral genetic exchanges in bacterial evolution and speciation.

Results: Here we analyzed the twelve sequenced genomes of Streptococcus pyogenes by a naïve approach that examines the preferential nucleotide usage along the chromosome, namely the usage of G versus C (GC-skew) and T versus A (TA-skew). The cumulative GC-skew plot presented an inverted V-shape composed of two symmetrical linear segments, where the minimum and maximum corresponded to the origin and terminus of DNA replication. In contrast, the cumulative TA-skew presented a V-shape, which segments were interrupted by several steep slopes regions (SSRs), indicative of a different nucleotide composition bias. Each S. pyogenes genome contained up to nine individual SSRs, encompassing all described strain-specific prophages. In addition, each genome contained a similar unique non-phage SSR, the core of which consisted of 31 highly homologous genes. This core includes the M-protein, other mga-related factors and other virulence genes, totaling ten intrinsic virulence genes. In addition to a high content in virulence-related genes and to a peculiar nucleotide bias, this SSR, which is 47 kb-long in a M1GAS strain, harbors direct repeats and a tRNA gene, suggesting a mobile element. Moreover, its complete absence in a M-protein negative group A Streptococcus natural isolate demonstrates that it could be spontaneously lost, but in vitro deletion experiments indicates that its excision occurred at very low rate. The stability of this SSR, combined to its presence in all sequenced S. pyogenes sequenced genome, suggests that it results from an ancient acquisition.

Conclusion: Thus, this non-phagic SSR is compatible with a pathogenicity island, acquired before S. pyogenes speciation. Its potential excision might bear relevance for vaccine development, because vaccines targeting M-protein might select for M-protein-negative variants that still carry other virulence determinants.

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TA skews (as in Fig. 1) for the twelve available genomes of S. pyogenes (see Table 1). Each tick mark on the vertical axes indicates 2000 T over A excess. Phagic SSRs are represented by grey rectangles while the conserved non-phagic SSR is outlined by boxed orange rectangles. In MGAS2096, MGAS6180 and MGAS10750, peculiar regions not documented as phages and presenting a different TA skew are shown with a green dotted box. These three regions are discussed in the text. Eventually, SSRs that are not described as prophages, but resemble mobile elements, are also present in the genomes of MGAS10750 and MGAS2096 and are the purpose of further studies. Phage numbering follows the order on the chromosome: in MGAS9429, 1 stands for phage 9429.1, 2 stands for phage 9429.2, etc (see references in Table 1).
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Figure 2: TA skews (as in Fig. 1) for the twelve available genomes of S. pyogenes (see Table 1). Each tick mark on the vertical axes indicates 2000 T over A excess. Phagic SSRs are represented by grey rectangles while the conserved non-phagic SSR is outlined by boxed orange rectangles. In MGAS2096, MGAS6180 and MGAS10750, peculiar regions not documented as phages and presenting a different TA skew are shown with a green dotted box. These three regions are discussed in the text. Eventually, SSRs that are not described as prophages, but resemble mobile elements, are also present in the genomes of MGAS10750 and MGAS2096 and are the purpose of further studies. Phage numbering follows the order on the chromosome: in MGAS9429, 1 stands for phage 9429.1, 2 stands for phage 9429.2, etc (see references in Table 1).

Mentions: The cumulative GC-skews of the other eleven S. pyogenes chromosomes are similar to that shown in Fig. 1A (data not presented). In contrast, the cumulative TA-skews are quite different both in terms of smoothness and in inter-strain variability (Fig. 1B and Fig. 2). Although both chromosomal arms conserve their symmetry, their slopes are opposite in TA- and GC-skews. Moreover, the two segments of the TA skew curves are interrupted by segments of steeper slopes, referred to as steep-slopes regions (SSR). These SSRs identify regions exhibiting different nucleotide composition than the core genome, and thus may highlight DNA segments of different origins.


M-protein and other intrinsic virulence factors of Streptococcus pyogenes are encoded on an ancient pathogenicity island.

Panchaud A, Guy L, Collyn F, Haenni M, Nakata M, Podbielski A, Moreillon P, Roten CA - BMC Genomics (2009)

TA skews (as in Fig. 1) for the twelve available genomes of S. pyogenes (see Table 1). Each tick mark on the vertical axes indicates 2000 T over A excess. Phagic SSRs are represented by grey rectangles while the conserved non-phagic SSR is outlined by boxed orange rectangles. In MGAS2096, MGAS6180 and MGAS10750, peculiar regions not documented as phages and presenting a different TA skew are shown with a green dotted box. These three regions are discussed in the text. Eventually, SSRs that are not described as prophages, but resemble mobile elements, are also present in the genomes of MGAS10750 and MGAS2096 and are the purpose of further studies. Phage numbering follows the order on the chromosome: in MGAS9429, 1 stands for phage 9429.1, 2 stands for phage 9429.2, etc (see references in Table 1).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2683870&req=5

Figure 2: TA skews (as in Fig. 1) for the twelve available genomes of S. pyogenes (see Table 1). Each tick mark on the vertical axes indicates 2000 T over A excess. Phagic SSRs are represented by grey rectangles while the conserved non-phagic SSR is outlined by boxed orange rectangles. In MGAS2096, MGAS6180 and MGAS10750, peculiar regions not documented as phages and presenting a different TA skew are shown with a green dotted box. These three regions are discussed in the text. Eventually, SSRs that are not described as prophages, but resemble mobile elements, are also present in the genomes of MGAS10750 and MGAS2096 and are the purpose of further studies. Phage numbering follows the order on the chromosome: in MGAS9429, 1 stands for phage 9429.1, 2 stands for phage 9429.2, etc (see references in Table 1).
Mentions: The cumulative GC-skews of the other eleven S. pyogenes chromosomes are similar to that shown in Fig. 1A (data not presented). In contrast, the cumulative TA-skews are quite different both in terms of smoothness and in inter-strain variability (Fig. 1B and Fig. 2). Although both chromosomal arms conserve their symmetry, their slopes are opposite in TA- and GC-skews. Moreover, the two segments of the TA skew curves are interrupted by segments of steeper slopes, referred to as steep-slopes regions (SSR). These SSRs identify regions exhibiting different nucleotide composition than the core genome, and thus may highlight DNA segments of different origins.

Bottom Line: The stability of this SSR, combined to its presence in all sequenced S. pyogenes sequenced genome, suggests that it results from an ancient acquisition.Thus, this non-phagic SSR is compatible with a pathogenicity island, acquired before S. pyogenes speciation.Its potential excision might bear relevance for vaccine development, because vaccines targeting M-protein might select for M-protein-negative variants that still carry other virulence determinants.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Fundamental Microbiology, University of Lausanne, Quartier UNIL-Sorge, Bâtiment Biophore, Lausanne, Switzerland. panchaud@u.washington.edu

ABSTRACT

Background: The increasing number of completely sequenced bacterial genomes allows comparing their architecture and genetic makeup. Such new information highlights the crucial role of lateral genetic exchanges in bacterial evolution and speciation.

Results: Here we analyzed the twelve sequenced genomes of Streptococcus pyogenes by a naïve approach that examines the preferential nucleotide usage along the chromosome, namely the usage of G versus C (GC-skew) and T versus A (TA-skew). The cumulative GC-skew plot presented an inverted V-shape composed of two symmetrical linear segments, where the minimum and maximum corresponded to the origin and terminus of DNA replication. In contrast, the cumulative TA-skew presented a V-shape, which segments were interrupted by several steep slopes regions (SSRs), indicative of a different nucleotide composition bias. Each S. pyogenes genome contained up to nine individual SSRs, encompassing all described strain-specific prophages. In addition, each genome contained a similar unique non-phage SSR, the core of which consisted of 31 highly homologous genes. This core includes the M-protein, other mga-related factors and other virulence genes, totaling ten intrinsic virulence genes. In addition to a high content in virulence-related genes and to a peculiar nucleotide bias, this SSR, which is 47 kb-long in a M1GAS strain, harbors direct repeats and a tRNA gene, suggesting a mobile element. Moreover, its complete absence in a M-protein negative group A Streptococcus natural isolate demonstrates that it could be spontaneously lost, but in vitro deletion experiments indicates that its excision occurred at very low rate. The stability of this SSR, combined to its presence in all sequenced S. pyogenes sequenced genome, suggests that it results from an ancient acquisition.

Conclusion: Thus, this non-phagic SSR is compatible with a pathogenicity island, acquired before S. pyogenes speciation. Its potential excision might bear relevance for vaccine development, because vaccines targeting M-protein might select for M-protein-negative variants that still carry other virulence determinants.

Show MeSH
Related in: MedlinePlus