Genomic analyses of the Chlamydia trachomatis core genome show an association between chromosomal genome, plasmid type and disease

Abstract

BackgroundChlamydia trachomatis (Ct) plasmid has been shown to encode genes essential for infection. We evaluated the population structure of Ct using whole-genome sequence data (WGS). In particular, the relationship between the Ct genome, plasmid and disease was investigated.ResultsWGS data from 157 Ct isolates deposited in the Chlamydiales pubMLST database (http://pubMLST.org/chlamydiales/) were annotated with 902 genes including the core and accessory genome. Plasmid associated genes were annotated and a plasmid MLST scheme was defined allowing plasmid sequence types to be determined. Plasmid allelic variation was investigated. Phylogenetic relationships were examined using the Genome Comparator tool available in pubMLST. Phylogenetic analyses identified four distinct Ct core genome clusters and six plasmid clusters, with a strong association between the chromosomal genotype and plasmid. This in turn was linked to ompA genovars and disease phenotype. Horizontal genetic transfer of plasmids was observed for three urogenital-associated isolates, which possessed plasmids more commonly found in isolates resulting from ocular infections. The pgp3 gene was identified as the most polymorphic plasmid gene and pgp4 was the most conserved.ConclusionA strong association between chromosomal genome, plasmid type and disease was observed, consistent with previous studies. This suggests co-evolution of the Ct chromosome and their plasmids, but we confirmed that plasmid transfer can occur between isolates. These data provide a better understanding of the genetic diversity occurring across the Ct genome in association with the plasmid content.Electronic supplementary materialThe online version of this article (10.1186/s12864-018-4522-3) contains supplementary material, which is available to authorized users.

The Nature and Extent of Plasmid Variation in Chlamydia trachomatis

“…Indeed, we did not identify any SNPs that consistently differentiated ocular from urogenital trachoma isolates; the SNP found to be unique to ocular strains by Seth-Smith et al (2009) [16] was also found to occur in sporadic genotype G (G_S4658 and G_Ar246) and J (J_UK583676, J_UK35672, J_Soton72 and J_S42) isolates in the present dataset (these sequences were not available at the time of the earlier study). This reflects the close relatedness between these and trachoma (serovar A) plasmids previously noted [62], and may result from plasmid-swapping between strains, or recombination between plasmids; there is prior evidence of this from the present dataset [49]. Also, there is precedence for recombination between ocular and urogenital isolates [75] so the opportunity for genetic exchange must exist.…”

“…Advancements in genome sequencing technology over the past 20 years have shed light on many aspects of chlamydial biology and epidemiology, and with hundreds of whole genome sequences now in the public domain we have the ability to delve into the evolutionary history of C. trachomatis to a depth not previously possible. We now understand that modern lineages are the product of thousands of years of evolution rather than millions [49], and that the chlamydial plasmid has been vertically inherited throughout its evolutionary history, with very few instances of recombination or exchange between lineages [16,35,49,62]. Furthermore, through genetic manipulation and in vivo experiments, the role of each plasmid CDS in chlamydial virulence, regulation of gene expression and plasmid maintenance are gradually being revealed (Table 1).…”

“…Furthermore, through genetic manipulation and in vivo experiments, the role of each plasmid CDS in chlamydial virulence, regulation of gene expression and plasmid maintenance are gradually being revealed (Table 1). However, few studies have performed in-depth analyses on multiple C. trachomatis plasmid sequences [16,35,62,63], and most of these studies considered relatively few isolates (the largest study up until now included 157 sequences in their analysis [62]. In the present study, we analysed 524 C. trachomatis plasmid sequences, providing the largest in-depth study on chlamydia plasmid diversity to date.…”

“…Evidence that these CDS5 mutations have become fixed in the LGV biovar due to natural selection has yet to be provided, although attempts at investigating signs of selection in the C. trachomatis plasmid have been made using the dN/dS ratio [8,62]. Both studies found that although CDS5 had a dN/dS ratio indicative of positive selection (dN/dS > 1), this value was not statistically significant.…”

Chlamydiae from Down Under: The Curious Cases of Chlamydial Infections in Australia

“…Regarding molecular characterisation of sexually transmitted Ct strains, the knowledge gap is even more prominent. Globally, the emergence of new sexually transmitted strains and variants and their rapid spread indicate the need for more comprehensive molecular studies to better understand the Ct tissue tropism as well as epidemiological network structures [43][44][45]. Molecular assays targeting the ompA gene revealed that Ct genovars E and F are commonly found in Australian heterosexual men and women, while genovars G and D are the most common in MSM with genovar L2 also occurring [46].…”