Research article

Co-evolution of genomes and plasmids within Chlamydia trachomatis and the emergence in Sweden of a new variant strain

Helena MB Seth-Smith² , Simon R Harris² , Kenneth Persson³ , Pete Marsh⁴ , Andrew Barron² , Alexandra Bignell² , Carina Bjartling⁵ , Louise Clark² , Lesley T Cutcliffe¹ , Paul R Lambden¹ , Nicola Lennard² , Sarah J Lockey¹ , Michael A Quail² , Omar Salim¹ , Rachel J Skilton¹ , Yibing Wang¹ , Martin J Holland⁶ , Julian Parkhill² , Nicholas R Thomson² and Ian N Clarke^1,7

¹Molecular Microbiology Group, University Medical School, Southampton General Hospital, Southampton, SO16 6YD, UK

²The Pathogen Sequencing Unit, The Wellcome Trust Sanger Institute, Hinxton, Cambridge, CB10 1SA, UK

³Department of Clinical Microbiology, Malmo University Hospital, SE 205 02 Malmo, Sweden

⁴Health Protection Agency South East, Southampton General Hospital, Southampton, SO16 6YD, UK

⁵Department of Obstetrics and Gynaecology, Malmo University Hospital, SE 205 02, Malmo, Sweden

⁶Viral Diseases Programme, Medical Research Council PO Box 273, Banjul, The Gambia

⁷Clinical Research Unit, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, UK

author email corresponding author email

BMC Genomics 2009, 10:239doi:10.1186/1471-2164-10-239

Published:	21 May 2009

Abstract

Background

Chlamydia trachomatis is the most common cause of sexually transmitted infections globally and the leading cause of preventable blindness in the developing world. There are two biovariants of C. trachomatis: 'trachoma', causing ocular and genital tract infections, and the invasive 'lymphogranuloma venereum' strains. Recently, a new variant of the genital tract C. trachomatis emerged in Sweden. This variant escaped routine diagnostic tests because it carries a plasmid with a deletion. Failure to detect this strain has meant it has spread rapidly across the country provoking a worldwide alert. In addition to being a key diagnostic target, the plasmid has been linked to chlamydial virulence. Analysis of chlamydial plasmids and their cognate chromosomes was undertaken to provide insights into the evolutionary relationship between chromosome and plasmid. This is essential knowledge if the plasmid is to be continued to be relied on as a key diagnostic marker, and for an understanding of the evolution of Chlamydia trachomatis.

Results

The genomes of two new C. trachomatis strains were sequenced, together with plasmids from six C. trachomatis isolates, including the new variant strain from Sweden. The plasmid from the new Swedish variant has a 377 bp deletion in the first predicted coding sequence, abolishing the site used for PCR detection, resulting in negative diagnosis. In addition, the variant plasmid has a 44 bp duplication downstream of the deletion. The region containing the second predicted coding sequence is the most highly conserved region of the plasmids investigated. Phylogenetic analysis of the plasmids and chromosomes are fully congruent. Moreover this analysis also shows that ocular and genital strains diverged from a common C. trachomatis progenitor.

Conclusion

The evolutionary pathways of the chlamydial genome and plasmid imply that inheritance of the plasmid is tightly linked with its cognate chromosome. These data suggest that the plasmid is not a highly mobile genetic element and does not transfer readily between isolates. Comparative analysis of the plasmid sequences has revealed the most conserved regions that should be used to design future plasmid based nucleic acid amplification tests, to avoid diagnostic failures.