M-protein and other intrinsic virulence factors of <it>Streptococcus pyogenes </it>are encoded on an ancient pathogenicity island

• Main Authors: Nakata Masanobu, Haenni Marisa, Collyn François, Guy Lionel, Panchaud Alexandre, Podbielski Andreas, Moreillon Philippe, Roten Claude-Alain H
• Format: Article
• Language: English
• Published: BMC 2009-04-01
• Series: BMC Genomics
• Online Access: http://www.biomedcentral.com/1471-2164/10/198

<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Results</p> <p>Here we analyzed the twelve sequenced genomes of <it>Streptococcus pyogenes </it>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 <it>S. pyogenes </it>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 <it>mga</it>-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 <it>Streptococcus </it>natural isolate demonstrates that it could be spontaneously lost, but <it>in vitro </it>deletion experiments indicates that its excision occurred at very low rate. The stability of this SSR, combined to its presence in all sequenced <it>S. pyogenes </it>sequenced genome, suggests that it results from an ancient acquisition.</p> <p>Conclusion</p> <p>Thus, this non-phagic SSR is compatible with a pathogenicity island, acquired before <it>S. pyogenes </it>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.</p>