title: Complete genome sequence of Treponema pallidum ssp. pallidum strain SS14 determined with oligonucleotide arrays.
abstract: BACKGROUND
  Syphilis spirochete Treponema pallidum ssp. pallidum remains the enigmatic pathogen, since no virulence factors have been identified and the pathogenesis of the disease is poorly understood. Increasing rates of new syphilis cases per year have been observed recently.
  
  
  RESULTS
  The genome of the SS14 strain was sequenced to high accuracy by an oligonucleotide array strategy requiring hybridization to only three arrays (Comparative Genome Sequencing, CGS). Gaps in the resulting sequence were filled with targeted dideoxy-terminators (DDT) sequencing and the sequence was confirmed by whole genome fingerprinting (WGF). When compared to the Nichols strain, 327 single nucleotide substitutions (224 transitions, 103 transversions), 14 deletions, and 18 insertions were found. On the proteome level, the highest frequency of amino acid-altering substitution polymorphisms was in novel genes, while the lowest was in housekeeping genes, as expected by their evolutionary conservation. Evidence was also found for hypervariable regions and multiple regions showing intrastrain heterogeneity in the T. pallidum chromosome.
  
  
  CONCLUSIONS
  The observed genetic changes do not have influence on the ability of Treponema pallidum to cause syphilitic infection, since both SS14 and Nichols are virulent in rabbit. However, this is the first assessment of the degree of variation between the two syphilis pathogens and paves the way for phylogenetic studies of this fascinating organism.
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, One Baylor Plaza, Alkek N1619, Houston, TX 77030, USA. matej@med.muni.cz
authors.forename: Petra
authors.initials: P
authors.lastname: Matejková
authors.forename: Michal
authors.initials: M
authors.lastname: Strouhal
authors.forename: David
authors.initials: D
authors.lastname: Smajs
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Norris
authors.forename: Timothy
authors.initials: T
authors.lastname: Palzkill
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Petrosino
authors.forename: Erica
authors.initials: E
authors.lastname: Sodergren
authors.forename: Jason E
authors.initials: JE
authors.lastname: Norton
authors.forename: Jaz
authors.initials: J
authors.lastname: Singh
authors.forename: Todd A
authors.initials: TA
authors.lastname: Richmond
authors.forename: Michael N
authors.initials: MN
authors.lastname: Molla
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Albert
authors.forename: George M
authors.initials: GM
authors.lastname: Weinstock
mesh_terms: D000818:Animals; D002874:Chromosome Mapping; D016172:DNA Fingerprinting; D016680:Genome, Bacterial; D006801:Humans; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D016366:Open Reading Frames; D020641:Polymorphism, Single Nucleotide; D011817:Rabbits; D015203:Reproducibility of Results; D017422:Sequence Analysis, DNA; D013587:Syphilis / Q000382:microbiology; D014210:Treponema pallidum / Q000235:genetics* / Q000302:isolation & purification / Q000472:pathogenicity