1887

Abstract

is a major cause of bacterial sexually transmitted infections worldwide. In 2006, a new variant of (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 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 isolates, including a similar serovar E 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 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.

Loading

Article metrics loading...

/content/journal/micro/10.1099/mic.0.036830-0
2010-05-01
2019-09-20
Loading full text...

Full text loading...

/deliver/fulltext/micro/156/5/1394.html?itemId=/content/journal/micro/10.1099/mic.0.036830-0&mimeType=html&fmt=ahah

References

  1. Anagrius, C. & Loré, B. ( 2008; ). Clinical experiences of new variant Chlamydia trachomatis in a Swedish high prevalence county. In 24th International Union against Sexually Transmitted Infections – Europe conference, Milan, abstract FOC4.12.
  2. Belland, R. J., Scidmore, M. A., Crane, D. D., Hogan, D. M., Whitmire, W., McClarty, G. & Caldwell, H. D. ( 2001; ). Chlamydia trachomatis cytotoxicity associated with complete and partial cytotoxin genes. Proc Natl Acad Sci U S A 98, 13984–13989.[CrossRef]
    [Google Scholar]
  3. Berriman, M. & Rutherford, K. ( 2003; ). Viewing and annotating sequence data with Artemis. Brief Bioinform 4, 124–132.[CrossRef]
    [Google Scholar]
  4. Bjartling, C., Osser, S., Johnson, A. & Persson, K. ( 2009; ). Clinical manifestations and epidemiology of the new genetic variant of Chlamydia trachomatis. Sex Transm Dis 36, 529–535.[CrossRef]
    [Google Scholar]
  5. Caldwell, H. D., Wood, H., Crane, D., Bailey, R., Jones, R. B., Mabey, D., Maclean, I., Mohammed, Z., Peeling, R. & other authors ( 2003; ). Polymorphisms in Chlamydia trachomatis tryptophan synthase genes differentiate between genital and ocular isolates. J Clin Invest 111, 1757–1769.[CrossRef]
    [Google Scholar]
  6. Carlson, J. H., Porcella, S. F., McClarty, G. & Caldwell, H. D. ( 2005; ). Comparative genomic analysis of Chlamydia trachomatis oculotropic and genitotropic strains. Infect Immun 73, 6407–6418.[CrossRef]
    [Google Scholar]
  7. Carlson, J. H., Whitmire, W. M., Crane, D. D., Wicke, L., Virtaneva, K., Sturdevant, D. E., Kupko, J. J., III, Porcella, S. F., Martinez-Orengo, N. & other authors ( 2008; ). The Chlamydia trachomatis plasmid is a transcriptional regulator of chromosomal genes and a virulence factor. Infect Immun 76, 2273–2283.[CrossRef]
    [Google Scholar]
  8. Carver, T. J., Rutherford, K. M., Berriman, M., Rajandream, M. A., Barrell, B. G. & Parkhill, J. ( 2005; ). ACT: the Artemis comparison tool. Bioinformatics 21, 3422–3423.[CrossRef]
    [Google Scholar]
  9. de Barbeyrac, B., Raherison, S., Cado, S., Normandin, F., Clerc, M., Clairet, V., Bébéar, C. & Goulet, V. ( 2007; ). French situation concerning the Swedish Chlamydia trachomatis variant. Euro Surveill 12, E11–E12.
    [Google Scholar]
  10. Farencena, A., Comanducci, M., Donati, M., Ratti, G. & Cevenini, R. ( 1997; ). Characterization of a new isolate of Chlamydia trachomatis which lacks the common plasmid and has properties of biovar trachoma. Infect Immun 65, 2965–2969.
    [Google Scholar]
  11. Fredlund, H., Falk, L., Jurstrand, M. & Unemo, M. ( 2004; ). Molecular genetic methods for diagnosis and characterisation of Chlamydia trachomatis and Neisseria gonorrhoeae: impact on epidemiological surveillance and interventions. APMIS 112, 771–784.[CrossRef]
    [Google Scholar]
  12. Hadad, R., Fredlund, H. & Unemo, M. ( 2008; ). Evaluation of the new COBAS TaqMan CT Test v2.0 and impact on the proportion of new variant Chlamydia trachomatis by the introduction of diagnostics detecting new variant C. trachomatis in Örebro county, Sweden. Sex Transm Infect 85, 190–193.
    [Google Scholar]
  13. Hanna, L., Thygeson, P. & Jawetz, E. ( 1959; ). Elementary-body virus isolated from clinical trachoma in California. Science 130, 1339–1340.[CrossRef]
    [Google Scholar]
  14. Health Protection Agency (2008). New variant Chlamydia trachomatis in Scotland. HPS Weekly Report 42 (2008/39). http://www.hps.scot.nhs.uk/ewr/redirect.aspx?id=39092. Accession date: 10th January 2010.
  15. Herrmann, B., Törner, A., Low, N., Klint, M., Nilsson, A., Velicko, I., Söderblom, T. & Blaxhult, A. ( 2008; ). Emergence and spread of Chlamydia trachomatis variant, Sweden. Emerg Infect Dis 14, 1462–1465.[CrossRef]
    [Google Scholar]
  16. Hoffmann, S. & Jensen, J. S. ( 2007; ). Mutant Chlamydia trachomatis in Denmark. Euro Surveill 12, E7–E8.
    [Google Scholar]
  17. Jurstrand, M., Falk, L., Fredlund, H., Lindberg, M., Olcén, P., Andersson, S., Persson, K., Albert, J. & Bäckman, A. ( 2001; ). Characterization of Chlamydia trachomatis omp1 genotypes among sexually transmitted disease patients in Sweden. J Clin Microbiol 39, 3915–3919.[CrossRef]
    [Google Scholar]
  18. Jurstrand, M., Christerson, L., Klint, M., Fredlund, H., Unemo, M. & Herrmann, B. ( 2010; ). Characterization of Chlamydia trachomatis by ompA sequencing and multilocus sequence typing in a Swedish county before and after identification of the new variant. Sex Transm Infect 86, 56–60.[CrossRef]
    [Google Scholar]
  19. Kleba, B. & Stephens, R. S. ( 2008; ). Chlamydial effector proteins localized to the host cell cytoplasmic compartment. Infect Immun 76, 4842–4850.[CrossRef]
    [Google Scholar]
  20. Klint, M., Fuxelius, H. H., Goldkuhl, R. R., Skarin, H., Rutemark, C., Andersson, S. G., Persson, K. & Herrmann, B. ( 2007; ). High-resolution genotyping of Chlamydia trachomatis strains by multilocus sequence analysis. J Clin Microbiol 45, 1410–1414.[CrossRef]
    [Google Scholar]
  21. Klint, M., Hadad, R., Christerson, L., Loré, B., Anagrius, C., Österlund, A., Larsson, I., Sylvan, S., Hallén, A. & other authors ( 2009; ). Spread of the new variant of Chlamydia trachomatis within Sweden over time. In 18th International Society for Sexually Transmitted Disease Research conference, London, United Kingdom, abstract P3.33.
  22. Lenart, J., Andersen, A. A. & Rockey, D. D. ( 2001; ). Growth and development of tetracycline-resistant Chlamydia suis. Antimicrob Agents Chemother 45, 2198–2203.[CrossRef]
    [Google Scholar]
  23. Lynagh, Y., Walsh, A. & Crowley, B. ( 2007; ). First report of the new variant strain of Chlamydia trachomatis in Ireland. EPI-Insight 8, 4. http://www.ndsc.ie/hpsc/EPI-Insight/Volume82007/File,2424,en.PDF. Accession date: 10th January 2010.
  24. Lysén, M., Österlund, A., Rubin, C.-J., Persson, T., Persson, I. & Herrmann, B. ( 2004; ). Characterization of ompA genotypes by sequence analysis of DNA from all detected cases of Chlamydia trachomatis infections during 1 year of contact tracing in a Swedish county. J Clin Microbiol 42, 1641–1647.[CrossRef]
    [Google Scholar]
  25. Marions, L., Rotzen-Östlund, M., Grillner, L., Edgardh, K., Tiveljung-Lindell, A., Wikström, A. & Lidbrink, P. ( 2008; ). High occurrence of a new variant of Chlamydia trachomatis escaping diagnostic tests among STI clinic patients in Stockholm, Sweden. Sex Transm Dis 35, 61–64.[CrossRef]
    [Google Scholar]
  26. Matsumoto, A., Izutsu, H., Miyashita, N. & Ohuchi, M. ( 1998; ). Plaque formation by and plaque cloning of Chlamydia trachomatis biovar trachoma. J Clin Microbiol 36, 3013–3019.
    [Google Scholar]
  27. Moghaddam, A. & Reinton, N. ( 2007; ). Identification of the Swedish Chlamydia trachomatis variant among patients attending a STI clinic in Oslo, Norway. Euro Surveill 12, E070301.3
    [Google Scholar]
  28. Pedersen, L. N., Pødenphant, L. & Møller, J. K. ( 2008; ). Highly discriminative genotyping of Chlamydia trachomatis using omp1 and a set of variable number tandem repeats. Clin Microbiol Infect 14, 644–652.[CrossRef]
    [Google Scholar]
  29. Pedersen, L. N., Herrmann, B. & Møller, J. K. ( 2009; ). Typing Chlamydia trachomatis: from egg yolk to nanotechnology. FEMS Immunol Med Microbiol 55, 120–130.[CrossRef]
    [Google Scholar]
  30. Peterson, E. M., Markoff, B. A., Schachter, J. & de la Maza, L. M. ( 1990; ). The 7.5-kb plasmid present in Chlamydia trachomatis is not essential for the growth of this microorganism. Plasmid 23, 144–148.[CrossRef]
    [Google Scholar]
  31. Pickett, M. A., Everson, J. S., Pead, P. J. & Clarke, I. N. ( 2005; ). The plasmids of Chlamydia trachomatis and Chlamydophila pneumoniae (N16): accurate determination of copy number and the paradoxical effect of plasmid-curing agents. Microbiology 151, 893–903.[CrossRef]
    [Google Scholar]
  32. Reinton, N., Moi, H., Bjerner, J. & Moghaddam, A. ( 2009; ). The Chlamydia mutant nvC. trachomatis in Norway. In 18th International Society for Sexually Transmitted Disease Research conference, London, United Kingdom, abstract P3.34.
  33. Reischl, U., Straube, E. & Unemo, M. ( 2009; ). The Swedish new variant of Chlamydia trachomatis (nvCT) remains undetected by many European laboratories as revealed in the recent PCR/NAT ring trial organised by INSTAND e.V., Germany. Euro Surveill 14, pii: 19302.
    [Google Scholar]
  34. Ripa, T. & Nilsson, P. A. ( 2006; ). A variant of Chlamydia trachomatis with deletion in cryptic plasmid: implications for use of PCR diagnostic tests. Euro Surveill 11, E061109.2.
    [Google Scholar]
  35. Ripa, T. & Nilsson, P. A. ( 2007; ). A Chlamydia trachomatis strain with a 377-bp deletion in the cryptic plasmid causing false-negative nucleic amplification tests. Sex Transm Dis 34, 255–256.
    [Google Scholar]
  36. Rockey, D. D., Lenart, J. & Stephens, R. S. ( 2000; ). Genome sequencing and our understanding of chlamydiae. Infect Immun 68, 5473–5479.[CrossRef]
    [Google Scholar]
  37. Schachter, J. & Meyer, K. F. ( 1969; ). Lymphogranuloma venereum. II. Characterization of some recently isolated strains. J Bacteriol 99, 636–638.
    [Google Scholar]
  38. Seth-Smith, H. M. B., Harris, S. R., Persson, K., Marsh, P., Barron, A., Bignell, A., Bjartling, C., Clark, L., Cutcliffe, L. T. & other authors ( 2009; ). Co-evolution of genomes and plasmids within Chlamydia trachomatis and the emergence in Sweden of a new variant strain. BMC Genomics 10, 239 [CrossRef]
    [Google Scholar]
  39. Skilton, R. J., Cutcliffe, L. T., Barlow, D., Wang, Y., Salim, O., Lambden, P. R. & Clarke, I. N. ( 2009; ). Penicillin induced persistence in Chlamydia trachomatis: high quality time lapse video analysis of the developmental cycle. PloS One 6, e7723.
  40. Skipp, P., Robinson, J., O'Connor, C. D. & Clarke, I. N. ( 2005; ). Shotgun proteomic analysis of Chlamydia trachomatis. Proteomics 5, 1558–1573.[CrossRef]
    [Google Scholar]
  41. Söderblom, T., Blaxhult, A., Fredlund, H. & Herrmann, B. ( 2006; ). Impact of a genetic variant of Chlamydia trachomatis on national detection rates in Sweden. Euro Surveill 11, E061207.1
    [Google Scholar]
  42. Stephens, R. S., Kalman, S., Lammel, C., Fan, J., Marathe, R., Aravind, L., Mitchell, W., Olinger, L., Tatusov, R. L. & other authors ( 1998; ). Genome sequence of an obligate intracellular pathogen of humans: Chlamydia trachomatis. Science 282, 754–759.[CrossRef]
    [Google Scholar]
  43. Stothard, D. R., Williams, J. A., Van der Pol, B. & Jones, R. B. ( 1998; ). Identification of a Chlamydia trachomatis serovar E urogenital isolate which lacks the cryptic plasmid. Infect Immun 66, 6010–6013.
    [Google Scholar]
  44. Suchland, R. J., Eckert, L. O., Hawes, S. E. & Stamm, W. E. ( 2003; ). Longitudinal assessment of infecting serovars of Chlamydia trachomatis in Seattle public health clinics: 1988–1996. Sex Transm Dis 30, 357–361.[CrossRef]
    [Google Scholar]
  45. Swedish Institute for Infectious Disease Control (SMI) ( 2009; ). Data and Statistics. http://www.smittskyddsinstitutet.se/in-english/statistics/. Accession date: 10th January 2010.
  46. Thomas, N. S., Lusher, M., Storey, C. C. & Clarke, I. N. ( 1997; ). Plasmid diversity in Chlamydia. Microbiology 143, 1847–1854.[CrossRef]
    [Google Scholar]
  47. Thomson, N. R., Holden, M. T., Carder, C., Lennard, N., Lockey, S. J., Marsh, P., Skipp, P., O'Connor, C. D., Goodhead, I. & other authors ( 2008; ). Chlamydia trachomatis: genome sequence analysis of lymphogranuloma venereum isolates. Genome Res 18, 161–171.
    [Google Scholar]
  48. Unemo, M., Olcén, P., Agné-Stadling, I., Feldt, A., Jurstrand, M., Herrmann, B., Persson, K., Nilsson, P., Ripa, T. & Fredlund, H. ( 2007; ). Experiences with the new genetic variant of Chlamydia trachomatis in Örebro county, Sweden – proportion, characteristics and effective diagnostic solution in an emergent situation. Euro Surveill 12, E5–E6.
    [Google Scholar]
  49. Unemo, M., Rossouw, A., James, V. & Jenkins, C. ( 2009; ). Can the Swedish new variant of Chlamydia trachomatis (nvCT) be detected by UK NEQAS participants from seventeen European countries and five additional countries/regions in 2009? Euro Surveill 14, pii: 19206
    [Google Scholar]
  50. Velicko, I., Kühlmann-Berenzon, S. & Blaxhult, A. ( 2007; ). Reasons for the sharp increase of genital chlamydia infections reported in the first months of 2007 in Sweden. Euro Surveill 12, E5–E6.
    [Google Scholar]
  51. Wang, S. A., Papp, J. R., Stamm, W. E., Peeling, S. W., Martin, D. H. & Holmes, K. K. ( 2005; ). Evaluation of antimicrobial resistance and treatment failures for Chlamydia trachomatis: a meeting report. J Infect Dis 191, 917–923.[CrossRef]
    [Google Scholar]
  52. Ward, M. E. ( 1983; ). Chlamydial classification, development and structure. Br Med Bull 39, 109–115.
    [Google Scholar]
  53. Westh, H. & Jensen, J. S. ( 2008; ). Low prevalence of the new variant of Chlamydia trachomatis in Denmark. Sex Transm Infect 84, 546–547.[CrossRef]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/micro/10.1099/mic.0.036830-0
Loading
/content/journal/micro/10.1099/mic.0.036830-0
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error