PT - JOURNAL ARTICLE AU - Simon R. Harris AU - Carl Robinson AU - Karen F. Steward AU - Katy S. Webb AU - Romain Paillot AU - Julian Parkhill AU - Matthew T. G. Holden AU - Andrew S. Waller TI - Genome specialization and decay of the strangles pathogen, <em>Streptococcus equi</em>, is driven by persistent infection AID - 10.1101/014118 DP - 2015 Jan 01 TA - bioRxiv PG - 014118 4099 - http://biorxiv.org/content/early/2015/01/22/014118.short 4100 - http://biorxiv.org/content/early/2015/01/22/014118.full AB - Strangles, the most frequently diagnosed infectious disease of horses worldwide, is caused by Streptococcus equi. Despite its prevalence, the global diversity and mechanisms underlying the evolution of S. equi as a host-restricted pathogen remain poorly understood. Here we define the global population structure of this important pathogen and reveal a population replacement in the late 19th or early 20th century, contemporaneous with a spate of global conflicts. Our data reveal a dynamic genome that continues to mutate and decay, but also to amplify and acquire genes despite the organism having lost its natural competence and become host-restricted.The lifestyle of S. equi within the horse is defined by short-term acute disease, strangles, followed by long-term carriage. Population analysis reveals evidence of convergent evolution in isolates from post-acute disease samples, as a result of niche adaptation to persistent carriage within a host. Mutations that lead to metabolic streamlining and the loss of virulence determinants are more frequently found in carriage isolates, suggesting that the pathogenic potential of S. equi reduces as a consequence of long term residency within the horse post acute disease. An example of this is the deletion of the equibactin siderophore locus that is associated with iron acquisition, which occurs exclusively in carrier isolates, and renders S. equi significantly less able to cause acute disease in the natural host. We identify several loci that may similarly be required for the full virulence of S. equi, directing future research towards the development of new vaccines against this host-restricted pathogen.