Co-evolution of genomes and plasmids within Chlamydia trachomatis and the emergence in Sweden of a new variant strain.
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.
Seth-Smith
Helena M B
HM
Molecular Microbiology Group, University Medical School, Southampton General Hospital, Southampton, SO16 6YD, UK. hss@sanger.ac.uk
Harris
Simon R
SR
Persson
Kenneth
K
Marsh
Pete
P
Barron
Andrew
A
Bignell
Alexandra
A
Bjartling
Carina
C
Clark
Louise
L
Cutcliffe
Lesley T
LT
Lambden
Paul R
PR
Lennard
Nicola
N
Lockey
Sarah J
SJ
Quail
Michael A
MA
Salim
Omar
O
Skilton
Rachel J
RJ
Wang
Yibing
Y
Holland
Martin J
MJ
Parkhill
Julian
J
Thomson
Nicholas R
NR
Clarke
Ian N
IN
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
D004269:DNA, Bacterial