title: Co-evolution of genomes and plasmids within Chlamydia trachomatis and the emergence in Sweden of a new variant strain.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Molecular Microbiology Group, University Medical School, Southampton General Hospital, Southampton, SO16 6YD, UK. hss@sanger.ac.uk
authors.forename: Helena M B
authors.initials: HM
authors.lastname: Seth-Smith
authors.forename: Simon R
authors.initials: SR
authors.lastname: Harris
authors.forename: Kenneth
authors.initials: K
authors.lastname: Persson
authors.forename: Pete
authors.initials: P
authors.lastname: Marsh
authors.forename: Andrew
authors.initials: A
authors.lastname: Barron
authors.forename: Alexandra
authors.initials: A
authors.lastname: Bignell
authors.forename: Carina
authors.initials: C
authors.lastname: Bjartling
authors.forename: Louise
authors.initials: L
authors.lastname: Clark
authors.forename: Lesley T
authors.initials: LT
authors.lastname: Cutcliffe
authors.forename: Paul R
authors.initials: PR
authors.lastname: Lambden
authors.forename: Nicola
authors.initials: N
authors.lastname: Lennard
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Lockey
authors.forename: Michael A
authors.initials: MA
authors.lastname: Quail
authors.forename: Omar
authors.initials: O
authors.lastname: Salim
authors.forename: Rachel J
authors.initials: RJ
authors.lastname: Skilton
authors.forename: Yibing
authors.initials: Y
authors.lastname: Wang
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Holland
authors.forename: Julian
authors.initials: J
authors.lastname: Parkhill
authors.forename: Nicholas R
authors.initials: NR
authors.lastname: Thomson
authors.forename: Ian N
authors.initials: IN
authors.lastname: Clarke
mesh_terms: D015373:Bacterial Typing Techniques; D002692:Chlamydia trachomatis / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification; D004269:DNA, Bacterial / Q000235:genetics; D019143:Evolution, Molecular; D016680:Genome, Bacterial; D006801:Humans; D054643:INDEL Mutation; D010802:Phylogeny; D010957:Plasmids / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion; D013548:Sweden
chemical_list: D004269:DNA, Bacterial