The Swedish new variant of Chlamydia trachomatis: genome sequence, morphology, cell tropism and phenotypic characterization

Abstract

Chlamydia trachomatis is a major cause of bacterial sexually transmitted infections worldwide. In 2006, a new variant of C. trachomatis (nvCT), carrying a 377 bp deletion within the plasmid, was reported in Sweden. This deletion included the targets used by the commercial diagnostic systems from Roche and Abbott. The nvCT is clonal (serovar/genovar E) and it spread rapidly in Sweden, undiagnosed by these systems. The degree of spread may also indicate an increased biological fitness of nvCT. The aims of this study were to describe the genome of nvCT, to compare the nvCT genome to all available C. trachomatis genome sequences and to investigate the biological properties of nvCT. An early nvCT isolate (Sweden2) was analysed by genome sequencing, growth kinetics, microscopy, cell tropism assay and antimicrobial susceptibility testing. It was compared with relevant C. trachomatis isolates, including a similar serovar E C. trachomatis wild-type strain that circulated in Sweden prior to the initially undetected expansion of nvCT. The nvCT genome does not contain any major genetic polymorphisms – the genes for central metabolism, development cycle and virulence are conserved – or phenotypic characteristics that indicate any altered biological fitness. This is supported by the observations that the nvCT and wild-type C. trachomatis infections are very similar in terms of epidemiological distribution, and that differences in clinical signs are only described, in one study, in women. In conclusion, the nvCT does not appear to have any altered biological fitness. Therefore, the rapid transmission of nvCT in Sweden was due to the strong diagnostic selective advantage and its introduction into a high-frequency transmitting population.

Polymorphisms in Inc Proteins and Differential Expression ofincGenes among Chlamydia trachomatis Strains Correlate with Invasiveness and Tropism of Lymphogranuloma Venereum Isolates

“…The genomic sequences of different ocular, urogenital, and LGV strains exhibit Ͼ98% identity and a high degree of synteny (12,25,29,31,50,53,55,59,60). Therefore, the determinants of the different types of infection (invasive or noninvasive) and tissue tropism (eyes, genitals, and lymph nodes) must rely on the few genes present in some strains but not in others and on nucleotide differences which may lead either to proteins with disease group-specific amino acids or to differential gene expression.…”

“…Our studies suggest that a subset of Inc proteins quences of the inc, pmp, and housekeeping genes analyzed were from the available genomes of 51 C. trachomatis strains (12,25,29,31,50,53,55,59,60). The strains and corresponding genome accession numbers are listed in Table S1 in the supplemental material.…”

Chlamydia trachomatis Infection and Reproductive Health Outcomes in Women

“…Although the ompA gene of C. trachomatis evolves more rapidly than the remaining genome, and its product (MOMP) is exposed on the surface of EBs, there is no evidence that any genotypic C. trachomatis variant (MOMP serovars) has a greater capacity than other variants to spread or avoid the immune response and produce greater clinical severity (30,92). The possible roles of other C. trachomatis biomarkers, such as the polymorphic outer membrane autotransporter family of proteins (89), type III secretion system effectors (29), and the putative large cytotoxin (9) are currently being studied.…”

Ab Initio Structural Modeling of and Experimental Validation for Chlamydia trachomatis Protein CT296 Reveal Structural Similarity to Fe(II) 2-Oxoglutarate-Dependent Enzymes

“…This distance dramatically reduces the utility of protein function assignments as inferred by sequence similarity. As a result, Chlamydia trachomatis encodes a relative overabundance (ϳ25%) of proteins with little or no sequence similarity to functionally defined proteins (i.e., hypothetical proteins) (5,47,50,53).The three-dimensional structure of a protein can be very informative and useful in regard to understanding functional characteristics of proteins with unknown function. This is because the structure of a protein provides the precise molecular details that often facilitate experimental characterization of an expected function.…”