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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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Spontaneous excision of M1 S. pyogenes SF370. Mitogenic exotoxin Z (smeZ/spy1998) and putative PTS system enzyme IIC component (spy2050) are the two coding genes where the boundaries for the natural isolate of M-protein-negative group A streptococcus T11 can be found (T11 deletion). In two out of four individual cycled cultures, an amplicon compatible with the excision of most part of the 47-kb SSR element was detected as shown by the two deletions (deletion 1 and deletion 2). Both amplicons were 200 bp apart from the boundaries of the natural T11 isolates. The region defined by the TA skew analysis starts 4520 bp upstream of the 5'-end of smeZ, and ends 835 bp downstream of the 3' end of spy2050 (see additional file 1). Oligonucleotides SVC1-1, SVC1-2, SVC2-3, SVC2-4 are represented above the genes. A 0.5-kb scale is indicated.
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Figure 6: Spontaneous excision of M1 S. pyogenes SF370. Mitogenic exotoxin Z (smeZ/spy1998) and putative PTS system enzyme IIC component (spy2050) are the two coding genes where the boundaries for the natural isolate of M-protein-negative group A streptococcus T11 can be found (T11 deletion). In two out of four individual cycled cultures, an amplicon compatible with the excision of most part of the 47-kb SSR element was detected as shown by the two deletions (deletion 1 and deletion 2). Both amplicons were 200 bp apart from the boundaries of the natural T11 isolates. The region defined by the TA skew analysis starts 4520 bp upstream of the 5'-end of smeZ, and ends 835 bp downstream of the 3' end of spy2050 (see additional file 1). Oligonucleotides SVC1-1, SVC1-2, SVC2-3, SVC2-4 are represented above the genes. A 0.5-kb scale is indicated.

Mentions: Since the M-protein-containing 47-kb SSR might represent a horizontally acquired element, we sought both whether natural group A streptococci missing this segment might exist, and whether it could be lost from S. pyogenes grown in vitro. A natural isolate of M-protein-negative group A streptococcus (serotype T11) [32] was analyzed. PCR-amplification indicates that this strain lacks a large 43-kb region, which encompasses 92% of the 47-kb SSR as determined by its genometric boundaries (Additional file 1 and Fig. 6).


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)

Spontaneous excision of M1 S. pyogenes SF370. Mitogenic exotoxin Z (smeZ/spy1998) and putative PTS system enzyme IIC component (spy2050) are the two coding genes where the boundaries for the natural isolate of M-protein-negative group A streptococcus T11 can be found (T11 deletion). In two out of four individual cycled cultures, an amplicon compatible with the excision of most part of the 47-kb SSR element was detected as shown by the two deletions (deletion 1 and deletion 2). Both amplicons were 200 bp apart from the boundaries of the natural T11 isolates. The region defined by the TA skew analysis starts 4520 bp upstream of the 5'-end of smeZ, and ends 835 bp downstream of the 3' end of spy2050 (see additional file 1). Oligonucleotides SVC1-1, SVC1-2, SVC2-3, SVC2-4 are represented above the genes. A 0.5-kb scale is indicated.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 6: Spontaneous excision of M1 S. pyogenes SF370. Mitogenic exotoxin Z (smeZ/spy1998) and putative PTS system enzyme IIC component (spy2050) are the two coding genes where the boundaries for the natural isolate of M-protein-negative group A streptococcus T11 can be found (T11 deletion). In two out of four individual cycled cultures, an amplicon compatible with the excision of most part of the 47-kb SSR element was detected as shown by the two deletions (deletion 1 and deletion 2). Both amplicons were 200 bp apart from the boundaries of the natural T11 isolates. The region defined by the TA skew analysis starts 4520 bp upstream of the 5'-end of smeZ, and ends 835 bp downstream of the 3' end of spy2050 (see additional file 1). Oligonucleotides SVC1-1, SVC1-2, SVC2-3, SVC2-4 are represented above the genes. A 0.5-kb scale is indicated.
Mentions: Since the M-protein-containing 47-kb SSR might represent a horizontally acquired element, we sought both whether natural group A streptococci missing this segment might exist, and whether it could be lost from S. pyogenes grown in vitro. A natural isolate of M-protein-negative group A streptococcus (serotype T11) [32] was analyzed. PCR-amplification indicates that this strain lacks a large 43-kb region, which encompasses 92% of the 47-kb SSR as determined by its genometric boundaries (Additional file 1 and Fig. 6).

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