Advertisement

The Hidden Genomics of Chlamydia trachomatis

  • James Hadfield
  • Angèle Bénard
  • Daryl Domman
  • Nicholas Thomson
Chapter
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 412)

Abstract

The application of whole-genome sequencing has moved us on from sequencing single genomes to defining unravelling population structures in different niches, and at the -species, -serotype or even -genus level, and in local, national and global settings. This has been instrumental in cataloguing and revealing a huge a range of diversity in this bacterium, when at first we thought there was little. Genomics has challenged assumptions, added insight, as well as confusion and glimpses of truths. What is clear is that at a time when we start to realise the extent and nature of the diversity contained within a genus or a species like this, the huge depth of knowledge communities have developed, through cell biology, as well as the new found molecular approaches will be more precious than ever to link genotype to phenotype. Here we detail the technological developments and insights we have seen during the relatively short time since we began to see the hidden genome of Chlamydia trachomatis.

References

  1. Al-Rifai KM (1988) Trachoma through history. Int Ophthalmol 12(1):9–14CrossRefGoogle Scholar
  2. Amann R, Springer N, Schonhuber W, Ludwig W, Schmid EN, Muller KD, Michel R (1997) Obligate intracellular bacterial parasites of acanthamoebae related to Chlamydia spp. Appl Environ Microbiol 63(1):115–121PubMedPubMedCentralGoogle Scholar
  3. Andersson P, Klein M, Lilliebridge RA, Giffard PM (2013) Sequences of multiple bacterial genomes and a Chlamydia trachomatis genotype from direct sequencing of DNA derived from a vaginal swab diagnostic specimen. Clin Microbiol Infect 19(9):E405–E408. doi: 10.1111/1469-0691.12237CrossRefPubMedGoogle Scholar
  4. Bavoil PM, Wyrick PB (2006) Chlamydia genomics and pathogenesis. Horizon Scientific PressGoogle Scholar
  5. Blanco L, Bernad A, Lazaro JM, Martin G, Garmendia C, Salas M (1989) Highly efficient DNA synthesis by the phage phi 29 DNA polymerase. Symmetrical mode of DNA replication. J Biol Chem 264(15):8935–8940PubMedGoogle Scholar
  6. Brunelle BW, Sensabaugh GF (2006) The ompA gene in Chlamydia trachomatis differs in phylogeny and rate of evolution from other regions of the genome. Infect Immun 74(1):578–585. doi: 10.1128/IAI.74.1.578-585.2006CrossRefPubMedPubMedCentralGoogle Scholar
  7. Caldwell HD, Wood H, Crane D, Bailey R, Jones RB, Mabey D, McClarty G (2003) Polymorphisms in Chlamydia trachomatis tryptophan synthase genes differentiate between genital and ocular isolates. J Clin Invest 111(11):1757–1769. doi: 10.1172/JCI17993CrossRefPubMedPubMedCentralGoogle Scholar
  8. Carlson JH, Porcella SF, McClarty G, Caldwell HD (2005) Comparative genomic analysis of Chlamydia trachomatis oculotropic and genitotropic strains. Infect Immun 73(10):6407–6418. doi: 10.1128/IAI.73.10.6407-6418.2005CrossRefPubMedPubMedCentralGoogle Scholar
  9. Carlson JH, Whitmire WM, Crane DD, Wicke L, Virtaneva K, Sturdevant DE, Caldwell HD (2008) The Chlamydia trachomatis plasmid is a transcriptional regulator of chromosomal genes and a virulence factor. Infect Immun 76(6):2273–2283. doi: 10.1128/IAI.00102-08CrossRefPubMedPubMedCentralGoogle Scholar
  10. Chilamakuri CS, Lorenz S, Madoui MA, Vodak D, Sun J, Hovig E, Meza-Zepeda LA (2014) Performance comparison of four exome capture systems for deep sequencing. BMC Genom 15:449. doi: 10.1186/1471-2164-15-449CrossRefGoogle Scholar
  11. Christiansen MT, Brown AC, Kundu S, Tutill HJ, Williams R, Brown JR, Breuer J (2014) Whole-genome enrichment and sequencing of Chlamydia trachomatis directly from clinical samples. BMC Infect Dis 14:591. doi: 10.1186/s12879-014-0591-3CrossRefPubMedPubMedCentralGoogle Scholar
  12. Dean FB, Nelson JR, Giesler TL, Lasken RS (2001) Rapid amplification of plasmid and phage DNA using Phi 29 DNA polymerase and multiply-primed rolling circle amplification. Genome Res 11(6):1095–1099. doi: 10.1101/gr.180501CrossRefPubMedPubMedCentralGoogle Scholar
  13. DeMars R, Weinfurter J (2008) Interstrain gene transfer in Chlamydia trachomatis in vitro: mechanism and significance. J Bacteriol 190(5):1605–1614. doi: 10.1128/JB.01592-07CrossRefPubMedPubMedCentralGoogle Scholar
  14. Demars R, Weinfurter J, Guex E, Lin J, Potucek Y (2007) Lateral gene transfer in vitro in the intracellular pathogen Chlamydia trachomatis. J Bacteriol 189(3):991–1003. doi: 10.1128/JB.00845-06CrossRefPubMedGoogle Scholar
  15. Dixon B (1992) Northern Territory Aboriginal Eye Health Committee Inc. Biennial Report July 1990–June 1992 Centre for Disease Control, Department of Health, Northern Territory. http://nthealth.intersearch.com.au/cgi-bin/koha/opac-detail.pl?biblionumber=8482
  16. Domman D, Collingro A, Lagkouvardos I, Gehre L, Weinmaier T, Rattei T, Horn M (2014) Massive expansion of Ubiquitination-related gene families within the Chlamydiae. Mol Biol Evol 31(11):2890–2904. doi: 10.1093/molbev/msu227CrossRefPubMedPubMedCentralGoogle Scholar
  17. 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(7):2965–2969PubMedPubMedCentralGoogle Scholar
  18. Fehlner-Gardiner C, Roshick C, Carlson JH, Hughes S, Belland RJ, Caldwell HD, McClarty G (2002) Molecular basis defining human Chlamydia trachomatis tissue tropism. A possible role for tryptophan synthase. J Biol Chem 277(30):26893–26903. doi: 10.1074/jbc.M203937200CrossRefGoogle Scholar
  19. Garcia-Garcia G, Baux D, Faugere V, Moclyn M, Koenig M, Claustres M, Roux AF (2016) Assessment of the latest NGS enrichment capture methods in clinical context. Sci Rep 6:20948. doi: 10.1038/srep20948CrossRefPubMedPubMedCentralGoogle Scholar
  20. Gomes JP, Bruno WJ, Borrego MJ, Dean D (2004) Recombination in the genome of Chlamydia trachomatis involving the polymorphic membrane protein C gene relative to ompA and evidence for horizontal gene transfer. J Bacteriol 186(13):4295–4306. doi: 10.1128/JB.186.13.4295-4306.2004CrossRefPubMedPubMedCentralGoogle Scholar
  21. Gomes JP, Nunes A, Bruno WJ, Borrego MJ, Florindo C, Dean D (2006) Polymorphisms in the nine polymorphic membrane proteins of Chlamydia trachomatis across all serovars: evidence for serovar Da recombination and correlation with tissue tropism. J Bacteriol 188(1):275–286. doi: 10.1128/JB.188.1.275-286.2006CrossRefPubMedPubMedCentralGoogle Scholar
  22. Hadfield J, Harris SR, Seth-Smith HMB, Parmar S, Andersson P, Giffard PM, Thomson NR (2017) Comprehensive global genome dynamics of Chlamydia trachomatis show ancient diversification followed by contemporary mixing and recent lineage expansion. Genome Res. doi: 10.1101/gr.212647.116CrossRefPubMedPubMedCentralGoogle Scholar
  23. Harris SR, Clarke IN, Seth-Smith HM, Solomon AW, Cutcliffe LT, Marsh P,… Thomson NR (2012) Whole-genome analysis of diverse Chlamydia trachomatis strains identifies phylogenetic relationships masked by current clinical typing. Nat Genet 44(4):413–419, S411. doi: 10.1038/ng.2214CrossRefPubMedPubMedCentralGoogle Scholar
  24. Hayes LJ, Yearsley P, Treharne JD, Ballard RA, Fehler GH, Ward ME (1994) Evidence for naturally occurring recombination in the gene encoding the major outer membrane protein of lymphogranuloma venereum isolates of Chlamydia trachomatis. Infect Immun 62(12):5659–5663PubMedPubMedCentralGoogle Scholar
  25. Hogan RJ, Mathews SA, Mukhopadhyay S, Summersgill JT, Timms P (2004) Chlamydial persistence: beyond the biphasic paradigm. Infect Immun 72(4):1843–1855CrossRefGoogle Scholar
  26. Horn M (2008) Chlamydiae as symbionts in eukaryotes. Annu Rev Microbiol 62:113–131. doi: 10.1146/annurev.micro.62.081307.162818. Review PMID:18473699CrossRefPubMedGoogle Scholar
  27. Horn M, Collingro A, Schmitz-Esser S, Beier CL, Purkhold U, Fartmann B, Wagner M (2004) Illuminating the evolutionary history of chlamydiae. Science 304(5671):728–730. doi: 10.1126/science.1096330CrossRefPubMedPubMedCentralGoogle Scholar
  28. Horz HP, Scheer S, Vianna ME, Conrads G (2010) New methods for selective isolation of bacterial DNA from human clinical specimens. Anaerobe 16(1):47–53. doi: 10.1016/j.anaerobe.2009.04.009CrossRefPubMedGoogle Scholar
  29. Hosono S, Faruqi AF, Dean FB, Du Y, Sun Z, Wu X, Lasken RS (2003) Unbiased whole-genome amplification directly from clinical samples. Genome Res 13(5):954–964. doi: 10.1101/gr.816903CrossRefPubMedPubMedCentralGoogle Scholar
  30. Hybiske K, Stephens RS (2007) Mechanisms of host cell exit by the intracellular bacterium Chlamydia. Proc Natl Acad Sci U S A 104(27):11430–11435. doi: 10.1073/pnas.0703218104CrossRefPubMedPubMedCentralGoogle Scholar
  31. Jeffrey BM, Suchland RJ, Quinn KL, Davidson JR, Stamm WE, Rockey DD (2010) Genome sequencing of recent clinical Chlamydia trachomatis strains identifies loci associated with tissue tropism and regions of apparent recombination. Infect Immun 78(6):2544–2553. doi: 10.1128/IAI.01324-09CrossRefPubMedPubMedCentralGoogle Scholar
  32. Jeffrey BM, Suchland RJ, Eriksen SG, Sandoz KM, Rockey DD (2013) Genomic and phenotypic characterization of in vitro-generated Chlamydia trachomatis recombinants. BMC Microbiol 13:142. doi: 10.1186/1471-2180-13-142CrossRefPubMedPubMedCentralGoogle Scholar
  33. Joseph SJ, Didelot X, Gandhi K, Dean D, Read TD (2011) Interplay of recombination and selection in the genomes of Chlamydia trachomatis. Biol Direct 6:28. doi: 10.1186/1745-6150-6-28CrossRefPubMedPubMedCentralGoogle Scholar
  34. Joseph SJ, Didelot X, Rothschild J, de Vries HJ, Morre SA, Read TD, Dean D (2012) Population genomics of Chlamydia trachomatis: insights on drift, selection, recombination, and population structure. Mol Biol Evol 29(12):3933–3946. doi: 10.1093/molbev/mss198CrossRefPubMedPubMedCentralGoogle Scholar
  35. Joseph SJ, Li B, Ghonasgi T, Haase CP, Qin ZS, Dean D, Read TD (2014) Direct amplification, sequencing and profiling of Chlamydia trachomatis strains in single and mixed infection clinical samples. PLoS ONE 9(6):e99290. doi: 10.1371/journal.pone.0099290CrossRefPubMedPubMedCentralGoogle Scholar
  36. Kari L, Whitmire WM, Olivares-Zavaleta N, Goheen MM, Taylor LD, Carlson JH, Caldwell HD (2011) A live-attenuated chlamydial vaccine protects against trachoma in nonhuman primates. J Exp Med 208(11):2217–2223. doi: 10.1084/jem.20111266CrossRefPubMedPubMedCentralGoogle Scholar
  37. Lagkouvardos I, Weinmaier T, Lauro FM, Cavicchioli R, Rattei T, Horn M (2014) Integrating metagenomic and amplicon databases to resolve the phylogenetic and ecological diversity of the Chlamydiae. ISME J 8(1):115–125. doi: 10.1038/ismej.2013.142CrossRefPubMedGoogle Scholar
  38. Lasken RS (2012) Genomic sequencing of uncultured microorganisms from single cells. Nature Rev Microbiol 10:631–640CrossRefGoogle Scholar
  39. Liechti GW, Kuru E, Hall E, Kalinda A, Brun YV, VanNieuwenhze M, Maurelli AT (2014) A new metabolic cell-wall labelling method reveals peptidoglycan in Chlamydia trachomatis. Nature 506(7489):507–510. doi: 10.1038/nature12892CrossRefPubMedPubMedCentralGoogle Scholar
  40. Linz B, Windsor HM, McGraw JJ, Hansen LM, Gajewski JP, Tomsho LP, Marshall BJ (2014) A mutation burst during the acute phase of Helicobacter pylori infection in humans and rhesus macaques. Nat Commun 5:4165. doi: 10.1038/ncomms5165CrossRefPubMedGoogle Scholar
  41. Longbottom D, Coulter LJ (2003) Animal chlamydioses and zoonotic implications. J Comp Pathol 128(4):217–244CrossRefGoogle Scholar
  42. Michel CE, Roper KG, Divena MA, Lee HH, Taylor HR (2011) Correlation of clinical trachoma and infection in aboriginal communities. PLoS Negl Trop Dis 5(3):e986. doi: 10.1371/journal.pntd.0000986CrossRefPubMedPubMedCentralGoogle Scholar
  43. Millman KL, Tavare S, Dean D (2001) Recombination in the ompA gene but not the omcB gene of Chlamydia contributes to serovar-specific differences in tissue tropism, immune surveillance, and persistence of the organism. J Bacteriol 183(20):5997–6008. doi: 10.1128/JB.183.20.5997-6008.2001CrossRefPubMedPubMedCentralGoogle Scholar
  44. Newman L, Rowley J, Vander Hoorn S, Wijesooriya NS, Unemo M, Low N, Temmerman M (2015) Global estimates of the prevalence and incidence of four curable sexually transmitted infections in 2012 based on systematic review and global reporting. PLoS One 10(12):e0143304. doi: 10.1371/journal.pone.0143304CrossRefPubMedPubMedCentralGoogle Scholar
  45. O’Neill CE, Seth-Smith HM, Van Der Pol B, Harris SR, Thomson NR, Cutcliffe LT, Clarke IN (2013) Chlamydia trachomatis clinical isolates identified as tetracycline resistant do not exhibit resistance in vitro: whole-genome sequencing reveals a mutation in porB but no evidence for tetracycline resistance genes. Microbiology 159(Pt 4):748–756. doi: 10.1099/mic.0.065391-0CrossRefPubMedGoogle Scholar
  46. Peterson EM, Markoff BA, Schachter J, de la Maza LM (1990) The 7.5-kb plasmid present in Chlamydia trachomatis is not essential for the growth of this microorganism. Plasmid 23(2):144–148CrossRefGoogle Scholar
  47. Putman TE, Suchland RJ, Ivanovitch JD, Rockey DD (2013) Culture-independent sequence analysis of Chlamydia trachomatis in urogenital specimens identifies regions of recombination and in-patient sequence mutations. Microbiology 159(Pt 10):2109–2117. doi: 10.1099/mic.0.070029-0CrossRefPubMedPubMedCentralGoogle Scholar
  48. Read TD, Joseph SJ, Didelot X, Liang B, Patel L, Dean D (2013) Comparative analysis of Chlamydia psittaci genomes reveals the recent emergence of a pathogenic lineage with a broad host range. MBio 4(2):604–612. doi: 10.1128/mBio.00604-12CrossRefGoogle Scholar
  49. Read TD, Myers GS, Brunham RC, Nelson WC, Paulsen IT, Heidelberg J, Fraser CM (2003) Genome sequence of Chlamydophila caviae (Chlamydia psittaci GPIC): examining the role of niche-specific genes in the evolution of the Chlamydiaceae. Nucleic Acids Res 31(8):2134–2147CrossRefGoogle Scholar
  50. Rockey DD (2011) Unraveling the basic biology and clinical significance of the chlamydial plasmid. J Exp Med 208(11):2159–2162. doi: 10.1084/jem.20112088CrossRefPubMedPubMedCentralGoogle Scholar
  51. Sandoz KM, Rockey DD (2010) Antibiotic resistance in Chlamydiae. Future Microbiol 5(9):1427–1442. doi: 10.2217/fmb.10.96CrossRefPubMedPubMedCentralGoogle Scholar
  52. Schachter J, Caldwell HD (1980) Chlamydiae. Annu Rev Microbiol 34:285–309. doi: 10.1146/annurev.mi.34.100180.001441CrossRefPubMedGoogle Scholar
  53. Schachter J, Moncada J (2005) Lymphogranuloma venereum: how to turn an endemic disease into an outbreak of a new disease? Start looking. Sex Transm Dis 32(6):331–332CrossRefGoogle Scholar
  54. Seth-Smith HM, Harris SR, Persson K, Marsh P, Barron A, Bignell A, Clarke IN (2009) Co-evolution of genomes and plasmids within Chlamydia trachomatis and the emergence in Sweden of a new variant strain. BMC Genom 10:239. doi: 10.1186/1471-2164-10-239CrossRefGoogle Scholar
  55. Seth-Smith HM, Harris SR, Scott P, Parmar S, Marsh P, Unemo M, Thomson NR (2013a) Generating whole bacterial genome sequences of low-abundance species from complex samples with IMS-MDA. Nat Protoc 8(12):2404–2412. doi: 10.1038/nprot.2013.147CrossRefPubMedGoogle Scholar
  56. Seth-Smith HM, Harris SR, Skilton RJ, Radebe FM, Golparian D, Shipitsyna E, Thomson NR (2013b) Whole-genome sequences of Chlamydia trachomatis directly from clinical samples without culture. Genome Res 23(5):855–866. doi: 10.1101/gr.150037.112CrossRefPubMedPubMedCentralGoogle Scholar
  57. Song L, Carlson JH, Whitmire WM, Kari L, Virtaneva K, Sturdevant DE, Caldwell HD (2013) Chlamydia trachomatis plasmid-encoded Pgp4 is a transcriptional regulator of virulence-associated genes. Infect Immun 81(3):636–644. doi: 10.1128/IAI.01305-12CrossRefPubMedPubMedCentralGoogle Scholar
  58. Stephens RS, Kalman S, Lammel C, Fan J, Marathe R, Aravind L, Davis RW (1998) Genome sequence of an obligate intracellular pathogen of humans: Chlamydia trachomatis. Science 282(5389):754–759CrossRefGoogle Scholar
  59. Taylor LD, Nelson DE, Dorward DW, Whitmire WM, Caldwell HD (2010) Biological characterization of Chlamydia trachomatis plasticity zone MACPF domain family protein CT153. Infect Immun 78(6):2691–2699. doi: 10.1128/IAI.01455-09CrossRefPubMedPubMedCentralGoogle Scholar
  60. Taylor-Brown A, Vaughan L, Greub G, Timms P, Polkinghorne A (2015) Twenty years of research into Chlamydia-like organisms: a revolution in our understanding of the biology and pathogenicity of members of the phylum Chlamydiae. Pathog Dis 73(1):1–15. doi: 10.1093/femspd/ftu009CrossRefPubMedPubMedCentralGoogle Scholar
  61. Thomson NR, Clarke IN (2010) Chlamydia trachomatis: small genome, big challenges. Future Microbiol 5(4):555–561. doi: 10.2217/fmb.10.31CrossRefPubMedGoogle Scholar
  62. Thomson NR, Holden MT, Carder C, Lennard N, Lockey SJ, Marsh P, Clarke IN (2008) Chlamydia trachomatis: genome sequence analysis of lymphogranuloma venereum isolates. Genome Res 18(1):161–171. doi: 10.1101/gr.7020108CrossRefPubMedPubMedCentralGoogle Scholar
  63. Unemo M, Clarke IN (2011) The Swedish new variant of Chlamydia trachomatis. Curr Opin Infect Dis 24(1):62–69. doi: 10.1097/QCO.0b013e32834204d5CrossRefPubMedGoogle Scholar
  64. Unemo M, Seth-Smith HM, Cutcliffe LT, Skilton RJ, Barlow D, Goulding D, Clarke IN (2010) The Swedish new variant of Chlamydia trachomatis: genome sequence, morphology, cell tropism and phenotypic characterization. Microbiology 156(Pt 5):1394–1404. doi: 10.1099/mic.0.036830-0CrossRefPubMedPubMedCentralGoogle Scholar
  65. Wang Y, Cutcliffe LT, Skilton RJ, Persson K, Bjartling C, Clarke IN (2013) Transformation of a plasmid-free, genital tract isolate of Chlamydia trachomatis with a plasmid vector carrying a deletion in CDS6 revealed that this gene regulates inclusion phenotype. Pathog Dis 67(2):100–103. doi: 10.1111/2049-632X.12024CrossRefPubMedPubMedCentralGoogle Scholar
  66. Ward ME (1983) Chlamydial classification, development and structure. Br Med Bull 39(2):109–115CrossRefGoogle Scholar
  67. West SK, Rapoza P, Munoz B, Katala S, Taylor HR (1991) Epidemiology of ocular chlamydial infection in a trachoma-hyperendemic area. J Infect Dis 163(4):752–756CrossRefGoogle Scholar
  68. WHO-report (2014) WHO Alliance for the Global Elimination of Blinding Trachoma by the year 2020. Progress report on elimination of trachoma, 2013. Wkly Epidemiol Rec, 89(39), 421–428Google Scholar
  69. Yilmaz S, Singh AK (2012) Single cell genome sequencing. Curr Op Biotechnol 23:437–443CrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  • James Hadfield
    • 1
  • Angèle Bénard
    • 1
  • Daryl Domman
    • 1
  • Nicholas Thomson
    • 1
    • 2
  1. 1.Wellcome Trust Sanger InstituteWellcome Genome CampusHinxtonUK
  2. 2.London School of Hygiene and Tropical MedicineLondonUK

Personalised recommendations