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Genomic evidence for the evolution of Streptococcus equi: host restriction, increased virulence, and genetic exchange with human pathogens.

Holden MT, Heather Z, Paillot R, Steward KF, Webb K, Ainslie F, Jourdan T, Bason NC, Holroyd NE, Mungall K, Quail MA, Sanders M, Simmonds M, Willey D, Brooks K, Aanensen DM, Spratt BG, Jolley KA, Maiden MC, Kehoe M, Chanter N, Bentley SD, Robinson C, Maskell DJ, Parkhill J, Waller AS - PLoS Pathog. (2009)

Bottom Line: We sequenced and compared the genomes of S. equi 4047 and S. zooepidemicus H70 and screened S. equi and S. zooepidemicus strains from around the world to uncover evidence of the genetic events that have shaped the evolution of the S. equi genome and led to its emergence as a host-restricted pathogen.We also highlight that S. equi, S. zooepidemicus, and S. pyogenes share a common phage pool that enhances cross-species pathogen evolution.We conclude that the complex interplay of functional loss, pathogenic specialization, and genetic exchange between S. equi, S. zooepidemicus, and S. pyogenes continues to influence the evolution of these important streptococci.

View Article: PubMed Central - PubMed

Affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom.

ABSTRACT
The continued evolution of bacterial pathogens has major implications for both human and animal disease, but the exchange of genetic material between host-restricted pathogens is rarely considered. Streptococcus equi subspecies equi (S. equi) is a host-restricted pathogen of horses that has evolved from the zoonotic pathogen Streptococcus equi subspecies zooepidemicus (S. zooepidemicus). These pathogens share approximately 80% genome sequence identity with the important human pathogen Streptococcus pyogenes. We sequenced and compared the genomes of S. equi 4047 and S. zooepidemicus H70 and screened S. equi and S. zooepidemicus strains from around the world to uncover evidence of the genetic events that have shaped the evolution of the S. equi genome and led to its emergence as a host-restricted pathogen. Our analysis provides evidence of functional loss due to mutation and deletion, coupled with pathogenic specialization through the acquisition of bacteriophage encoding a phospholipase A(2) toxin, and four superantigens, and an integrative conjugative element carrying a novel iron acquisition system with similarity to the high pathogenicity island of Yersinia pestis. We also highlight that S. equi, S. zooepidemicus, and S. pyogenes share a common phage pool that enhances cross-species pathogen evolution. We conclude that the complex interplay of functional loss, pathogenic specialization, and genetic exchange between S. equi, S. zooepidemicus, and S. pyogenes continues to influence the evolution of these important streptococci.

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ClonalFrame analysis of MLST alleles of 26 S. equi and 140 S. zooepidemicus isolates and its relationship with the prevalence of selected differences between the Se4047 and SzH70 genomes.Genes examined were lacE, rbsD, sorD, SZO06680 (encoding a putative hyaluronate lyase and specific to the 4 bp missing from SEQ1479), srtC, srtD, SZO08560 (encoding a Listeria-Bacteroides repeat domain containing surface-anchored protein), esaA, SZO14370 (within the CRISPR locus), slaA, slaB, seeL, seeM, seeH, seeI, eqbE (within the equibactin locus), SEQ0235 (encoding Se18.9), and gyrA. Functional assays determined the ability of different isolates to ferment lactose, ribose, and sorbitol and to induce mitogenic responses in equine peripheral blood mononuclear cells. The number of isolates representing each ST is indicated. STs where all isolates contained the gene or possessed functional activity are shown in red, STs where all isolates lacked the gene or functionality are shown in blue, and STs containing some isolates containing the gene or functionality and some that did not are colored in yellow. The position of S. equi isolates and SzH70 are indicated. SzMGCS10565 is a single locus variant of ST-10 (ST-72; not shown), and had an identical gene prevalence profile to the ST-10 isolates based on in silico analysis of its genome sequence [12].
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ppat-1000346-g004: ClonalFrame analysis of MLST alleles of 26 S. equi and 140 S. zooepidemicus isolates and its relationship with the prevalence of selected differences between the Se4047 and SzH70 genomes.Genes examined were lacE, rbsD, sorD, SZO06680 (encoding a putative hyaluronate lyase and specific to the 4 bp missing from SEQ1479), srtC, srtD, SZO08560 (encoding a Listeria-Bacteroides repeat domain containing surface-anchored protein), esaA, SZO14370 (within the CRISPR locus), slaA, slaB, seeL, seeM, seeH, seeI, eqbE (within the equibactin locus), SEQ0235 (encoding Se18.9), and gyrA. Functional assays determined the ability of different isolates to ferment lactose, ribose, and sorbitol and to induce mitogenic responses in equine peripheral blood mononuclear cells. The number of isolates representing each ST is indicated. STs where all isolates contained the gene or possessed functional activity are shown in red, STs where all isolates lacked the gene or functionality are shown in blue, and STs containing some isolates containing the gene or functionality and some that did not are colored in yellow. The position of S. equi isolates and SzH70 are indicated. SzMGCS10565 is a single locus variant of ST-10 (ST-72; not shown), and had an identical gene prevalence profile to the ST-10 isolates based on in silico analysis of its genome sequence [12].

Mentions: Carbohydrate metabolism in streptococci plays an important role in colonization of mucosal surfaces [17]. Carbohydrate fermentation is also commonly used to differentiate S. equi strains from S. zooepidemicus [18]. Comparison of the genome sequences identified a 5 kb deletion in the Se4047 genome that partially deleted lacD and lacG and deleted lacE, lacF and lacT. Se4047 also contains a deletion of sorD immediately upstream of SEQ0286 and a deletion between SEQ0536 and SEQ0537 that spans the operon required for ribose fermentation. Specialization of S. equi has probably rendered these pathways redundant, resulting in their loss. To determine if differences in gene content identified through genome comparison represented variation between S. equi and S. zooepidemicus or variation within their populations, we screened by PCR a panel of S. equi and S. zooepidemicus strains that are representative of the wider population as defined by MLST [2]. This included 26 isolates of S. equi (representing 2 STs) and 140 isolates of S. zooepidemicus (representing 95 STs) [2]. All 26 S. equi strains examined lacked lacE, sorD and rbsD and the capacity to ferment lactose, sorbitol or ribose. However, only 15 (ST-7, ST-39, ST-57, ST-97 and ST-106) and 1 (ST-39) of 140 S. zooepidemicus isolates tested did not ferment ribose or sorbitol, respectively (Figure 4).


Genomic evidence for the evolution of Streptococcus equi: host restriction, increased virulence, and genetic exchange with human pathogens.

Holden MT, Heather Z, Paillot R, Steward KF, Webb K, Ainslie F, Jourdan T, Bason NC, Holroyd NE, Mungall K, Quail MA, Sanders M, Simmonds M, Willey D, Brooks K, Aanensen DM, Spratt BG, Jolley KA, Maiden MC, Kehoe M, Chanter N, Bentley SD, Robinson C, Maskell DJ, Parkhill J, Waller AS - PLoS Pathog. (2009)

ClonalFrame analysis of MLST alleles of 26 S. equi and 140 S. zooepidemicus isolates and its relationship with the prevalence of selected differences between the Se4047 and SzH70 genomes.Genes examined were lacE, rbsD, sorD, SZO06680 (encoding a putative hyaluronate lyase and specific to the 4 bp missing from SEQ1479), srtC, srtD, SZO08560 (encoding a Listeria-Bacteroides repeat domain containing surface-anchored protein), esaA, SZO14370 (within the CRISPR locus), slaA, slaB, seeL, seeM, seeH, seeI, eqbE (within the equibactin locus), SEQ0235 (encoding Se18.9), and gyrA. Functional assays determined the ability of different isolates to ferment lactose, ribose, and sorbitol and to induce mitogenic responses in equine peripheral blood mononuclear cells. The number of isolates representing each ST is indicated. STs where all isolates contained the gene or possessed functional activity are shown in red, STs where all isolates lacked the gene or functionality are shown in blue, and STs containing some isolates containing the gene or functionality and some that did not are colored in yellow. The position of S. equi isolates and SzH70 are indicated. SzMGCS10565 is a single locus variant of ST-10 (ST-72; not shown), and had an identical gene prevalence profile to the ST-10 isolates based on in silico analysis of its genome sequence [12].
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2654543&req=5

ppat-1000346-g004: ClonalFrame analysis of MLST alleles of 26 S. equi and 140 S. zooepidemicus isolates and its relationship with the prevalence of selected differences between the Se4047 and SzH70 genomes.Genes examined were lacE, rbsD, sorD, SZO06680 (encoding a putative hyaluronate lyase and specific to the 4 bp missing from SEQ1479), srtC, srtD, SZO08560 (encoding a Listeria-Bacteroides repeat domain containing surface-anchored protein), esaA, SZO14370 (within the CRISPR locus), slaA, slaB, seeL, seeM, seeH, seeI, eqbE (within the equibactin locus), SEQ0235 (encoding Se18.9), and gyrA. Functional assays determined the ability of different isolates to ferment lactose, ribose, and sorbitol and to induce mitogenic responses in equine peripheral blood mononuclear cells. The number of isolates representing each ST is indicated. STs where all isolates contained the gene or possessed functional activity are shown in red, STs where all isolates lacked the gene or functionality are shown in blue, and STs containing some isolates containing the gene or functionality and some that did not are colored in yellow. The position of S. equi isolates and SzH70 are indicated. SzMGCS10565 is a single locus variant of ST-10 (ST-72; not shown), and had an identical gene prevalence profile to the ST-10 isolates based on in silico analysis of its genome sequence [12].
Mentions: Carbohydrate metabolism in streptococci plays an important role in colonization of mucosal surfaces [17]. Carbohydrate fermentation is also commonly used to differentiate S. equi strains from S. zooepidemicus [18]. Comparison of the genome sequences identified a 5 kb deletion in the Se4047 genome that partially deleted lacD and lacG and deleted lacE, lacF and lacT. Se4047 also contains a deletion of sorD immediately upstream of SEQ0286 and a deletion between SEQ0536 and SEQ0537 that spans the operon required for ribose fermentation. Specialization of S. equi has probably rendered these pathways redundant, resulting in their loss. To determine if differences in gene content identified through genome comparison represented variation between S. equi and S. zooepidemicus or variation within their populations, we screened by PCR a panel of S. equi and S. zooepidemicus strains that are representative of the wider population as defined by MLST [2]. This included 26 isolates of S. equi (representing 2 STs) and 140 isolates of S. zooepidemicus (representing 95 STs) [2]. All 26 S. equi strains examined lacked lacE, sorD and rbsD and the capacity to ferment lactose, sorbitol or ribose. However, only 15 (ST-7, ST-39, ST-57, ST-97 and ST-106) and 1 (ST-39) of 140 S. zooepidemicus isolates tested did not ferment ribose or sorbitol, respectively (Figure 4).

Bottom Line: We sequenced and compared the genomes of S. equi 4047 and S. zooepidemicus H70 and screened S. equi and S. zooepidemicus strains from around the world to uncover evidence of the genetic events that have shaped the evolution of the S. equi genome and led to its emergence as a host-restricted pathogen.We also highlight that S. equi, S. zooepidemicus, and S. pyogenes share a common phage pool that enhances cross-species pathogen evolution.We conclude that the complex interplay of functional loss, pathogenic specialization, and genetic exchange between S. equi, S. zooepidemicus, and S. pyogenes continues to influence the evolution of these important streptococci.

View Article: PubMed Central - PubMed

Affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom.

ABSTRACT
The continued evolution of bacterial pathogens has major implications for both human and animal disease, but the exchange of genetic material between host-restricted pathogens is rarely considered. Streptococcus equi subspecies equi (S. equi) is a host-restricted pathogen of horses that has evolved from the zoonotic pathogen Streptococcus equi subspecies zooepidemicus (S. zooepidemicus). These pathogens share approximately 80% genome sequence identity with the important human pathogen Streptococcus pyogenes. We sequenced and compared the genomes of S. equi 4047 and S. zooepidemicus H70 and screened S. equi and S. zooepidemicus strains from around the world to uncover evidence of the genetic events that have shaped the evolution of the S. equi genome and led to its emergence as a host-restricted pathogen. Our analysis provides evidence of functional loss due to mutation and deletion, coupled with pathogenic specialization through the acquisition of bacteriophage encoding a phospholipase A(2) toxin, and four superantigens, and an integrative conjugative element carrying a novel iron acquisition system with similarity to the high pathogenicity island of Yersinia pestis. We also highlight that S. equi, S. zooepidemicus, and S. pyogenes share a common phage pool that enhances cross-species pathogen evolution. We conclude that the complex interplay of functional loss, pathogenic specialization, and genetic exchange between S. equi, S. zooepidemicus, and S. pyogenes continues to influence the evolution of these important streptococci.

Show MeSH
Related in: MedlinePlus