Comparative and Functional Genomic Analysis of <i>Streptococcus Equi</i> and <i>Streptococcus Zooepidemicus</i> : Identifying Novel Vaccine Targets

Streptococcus equi subspecies equi (<i>S. equi</i>) is a host-restricted pathogen of horses and the aetiological agent of strangles. Available evidence suggests that <i>S. equi</i> evolved from <i>Streptococcus equi</i> subspecies <i>zooepidemicus</i> (<i>S. zooepidemicus</i>), a versatile bacterium that is often isolated from the equine respiratory tract, but can cause opportunistic disease in horses and other animals. A comparison of the genomes of <i>S. equi</i> 4047 and <i>S. zooepidemicus</i> H70 and the screening of diverse <i>S. equi</i> and <i>S. zooepidemicus</i> strains uncovered the genetic events that have shaped the evolution of <i>S. equi</i>, and led to its emergence as a niche-adapted pathogen. This analysis provides evidence of functional loss, changes in the organisation and sequence of genes, and pathogenic specialisation through the acquisition of prophage encoding a phospholipase A2 toxin, and 4 superantigens, and an integrative conjugative element carrying a novel siderophore-like nonribosomal peptide synthetase (NRPS) system. The NRPS shares similarity with the yersiniabactin system found in the high pathogenicity island of <i>Yersinia pestis</i> and is the first of its kind to be identified in streptococci. As this genetic feature is absent from the <i>S. zooepidemicus</i> population, its gain is considered to have been a key event in the emergence of <i>S. equi</i>. Further work determined a role for the NRPS in iron acquisition, and through its heterologous reconstitution in <i>Escherichia coli</i> and/or the analysis of allelic replacement mutants in S. equi, identified biosynthetic genes, transporters involved in efflux and import of the NRPS product(s), salicylate as a substrate for the NRPS and its regulation by a novel iron-dependent IdeR-like repressor, using various <i>in vitro</i> growth assays, including sensitivity to streptonigrin and ⁵⁵Fe accumulation. Possible vaccine targets were identified in both subspecies and existing diagnostic tools were improved, which included the development of a quantitative PCR test for the detection of <i>S. equi</i>.

Name dc:type.qualificationname

phd

Level dc:type.qualificationlevel

doctoral

Grantor dc:publisher.institution

The Open University

Year dc:date.issued

2009

Author dc:creator

• Heather, Zoe

Language dc:language

en