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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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Diagram of the SZO08560 invertible promoter in SzH70.The promoter region of SZO08560 (−170 bp to −55 bp) is bordered by GTAGACTTTA and TAAAGTCTAC inverted repeats that invert to switch transcription from forward to reverse orientation.
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ppat-1000346-g005: Diagram of the SZO08560 invertible promoter in SzH70.The promoter region of SZO08560 (−170 bp to −55 bp) is bordered by GTAGACTTTA and TAAAGTCTAC inverted repeats that invert to switch transcription from forward to reverse orientation.

Mentions: The SzH70 and SzMGCS10565 genomes encode a 131 kDa putative surface protein containing 1,160 amino acids with an LPXTG motif (SZO08560 and Sez_1114). However, the Se4047 genome encodes only the final 112 amino acids of this protein (SEQ1307a) and lacks an adjacent gene predicted to encode a recombinase (SZO08550 and Sez_1116). SZO08560 and Sez_1114 share sequence similarity with hypothetical proteins of S. suis strain 05ZYH33 (SSU05_0473) and S. agalactiae strain COH1 (SAN_1519) and contain four Listeria-Bacteroides repeat Pfam domains (PF09479). The ∼70 amino acid residue repeats occur in a range of Gram-positive surface proteins including the InlA internalin of Listeria monocytogenes [34] (Figure S2). InlA interacts with E-cadherin to promote invasion of L. monocytogenes into particular host cells [35]. Examination of the SzH70 genome sequencing data revealed five sequence reads that positioned the promoter region of SZO08560 (−170 bp to −55 bp) in the reverse orientation. This sequence is bordered by GTAGACTTTA and TAAAGTCTAC inverted repeats and we propose that inversion of this sequence switches transcription of SZO08560 on or off, thereby modulating the production of this surface protein in a manner akin to phase variation in E. coli (Figure 5) [36]. Reverse transcription qPCR using RNA extracted from log-phase cultures of SzH70 and normalized for expression of the housekeeping gene gyrA demonstrated that the SZO08560 promoter of SzH70 transcribed 44-fold more RNA in the forward direction than the reverse. To our knowledge this is the first potential example of recombinase regulation of surface protein production in streptococci. None of the 26 isolates of S. equi, but 101 of 140 S. zooepidemicus isolates tested positive for SZO08560 by PCR. SzMGCS10565 contains an IS element between the inverted repeats bordering the Sez_1114 promoter and the recombinase (Sez_1116), the consequences of this on transcription of Sez_1114 are not yet known.


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)

Diagram of the SZO08560 invertible promoter in SzH70.The promoter region of SZO08560 (−170 bp to −55 bp) is bordered by GTAGACTTTA and TAAAGTCTAC inverted repeats that invert to switch transcription from forward to reverse orientation.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2654543&req=5

ppat-1000346-g005: Diagram of the SZO08560 invertible promoter in SzH70.The promoter region of SZO08560 (−170 bp to −55 bp) is bordered by GTAGACTTTA and TAAAGTCTAC inverted repeats that invert to switch transcription from forward to reverse orientation.
Mentions: The SzH70 and SzMGCS10565 genomes encode a 131 kDa putative surface protein containing 1,160 amino acids with an LPXTG motif (SZO08560 and Sez_1114). However, the Se4047 genome encodes only the final 112 amino acids of this protein (SEQ1307a) and lacks an adjacent gene predicted to encode a recombinase (SZO08550 and Sez_1116). SZO08560 and Sez_1114 share sequence similarity with hypothetical proteins of S. suis strain 05ZYH33 (SSU05_0473) and S. agalactiae strain COH1 (SAN_1519) and contain four Listeria-Bacteroides repeat Pfam domains (PF09479). The ∼70 amino acid residue repeats occur in a range of Gram-positive surface proteins including the InlA internalin of Listeria monocytogenes [34] (Figure S2). InlA interacts with E-cadherin to promote invasion of L. monocytogenes into particular host cells [35]. Examination of the SzH70 genome sequencing data revealed five sequence reads that positioned the promoter region of SZO08560 (−170 bp to −55 bp) in the reverse orientation. This sequence is bordered by GTAGACTTTA and TAAAGTCTAC inverted repeats and we propose that inversion of this sequence switches transcription of SZO08560 on or off, thereby modulating the production of this surface protein in a manner akin to phase variation in E. coli (Figure 5) [36]. Reverse transcription qPCR using RNA extracted from log-phase cultures of SzH70 and normalized for expression of the housekeeping gene gyrA demonstrated that the SZO08560 promoter of SzH70 transcribed 44-fold more RNA in the forward direction than the reverse. To our knowledge this is the first potential example of recombinase regulation of surface protein production in streptococci. None of the 26 isolates of S. equi, but 101 of 140 S. zooepidemicus isolates tested positive for SZO08560 by PCR. SzMGCS10565 contains an IS element between the inverted repeats bordering the Sez_1114 promoter and the recombinase (Sez_1116), the consequences of this on transcription of Sez_1114 are not yet known.

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