Chlamydia trachomatis is the most common cause of non
specific urethritis in the industrialised world, and the major
infectious cause of preventable blindness (trachoma) in the third world
[1,2]. C. trachomatis can be divided into at least 15 serovars or serotypes, distinguished by ompA sequencing , which are associated with different disease pathologies .
Serotypes A, B, Ba and C are generally associated with blinding
trachoma and serotypes D to K cause non-disseminating sexually
transmitted infections. These 12 serotypes are all naturally restricted
to infection of genital or ocular epithelial cells and have not been
observed to be invasive .
By contrast, serotypes L1, L2 and L3 cause a rare invasive and systemic
sexually transmitted infection normally found in the tropics, known as
lymphogranuloma venereum (LGV) [6,7].
In October 2006 a new variant of C. trachomatis was
described in Sweden that evaded several of the then current commercial
molecular diagnostic tests for detecting the microorganism, which were
based on the presence of specific plasmid sequences .
A deletion of 377 bp of plasmid DNA, in the region used for nucleic
acid amplification tests (NAATs), is responsible for the negative
diagnoses . All new variant strains of C. trachomatis belong to serotype E .
Failure to detect the plasmid and hence treat those infected with the
new variant has led to a significant increase in cases, and in some
Swedish counties 20 – 64% of current infections are caused by this
strain of C. trachomatis .
Strains of C. trachomatis have a highly conserved small genome of approximately 1 Mb and harbour a plasmid of approximately 7 kb . Some plasmid-free isolates of C. trachomatis have
been described, but these are exceedingly rare and the only viable
clinical isolates described that are plasmid free belong to serotypes
L2, D and E [12-14]. The C. trachomatis plasmids
sequenced to date each contain eight predicted coding sequences (CDSs),
along with a set of four 22 bp repeats which is understood to be the
origin of replication [15,16].
Characterization of plasmid functions and of chlamydial genes in
general has been greatly impeded by the lack of a genetic system for
studying C. trachomatis  and so little is known about the function of these CDSs beyond in silico predictions
of function for 5 CDSs and the observation that the CDS previously
designated ORF5 encodes a protein of 28 kDa (pgp3) when expressed in Escherichia coli [18,19].
However, the role of pgp3 in the chlamydial developmental cycle and the
overall biological function of the plasmid remains unknown.
Since the study of C. trachomatis genes is hampered by the
lack of any molecular tools with which to manipulate strains, the
emergence of the new variant strain and naturally occurring mutants
provides an opportunity to investigate the evolution of the plasmids
and to determine whether the evolutionary pathway of these plasmids
matches that of the chromosome. In this study the nature and extent of
chromosome and plasmid variation in C. trachomatis has been
investigated. To extend the current dataset, two isolates of the
previously unsequenced serotype B were completely sequenced, as were
four plasmids from Swedish strains belonging to serotypes E and F,
including that of the new variant strain. The plasmid is useful as a
target for diagnostic testing because it is relatively stable and hence
more resistant to nuclease damage than the genome, and present at up to
ten copies per genome .
Thus a detailed knowledge of the sequence conservation and the
stability of chlamydial plasmids will be critically informative in
determining whether the plasmid is a reliable target for future