Complete Genome Sequence and Annotation of the
            <i>Treponema pallidum</i>
            subsp.
            <i>pallidum</i>
            Chicago Strain

Giacani, Lorenzo; Jeffrey, Brendan M.; Molini, Barbara J.; Le, Hoavan T.; Lukehart, Sheila A.; Centurión-Lara, Arturo; Rockey, Daniel D.

doi:10.1128/jb.00159-10

Cited by 54 publications

(65 citation statements)

References 11 publications

(9 reference statements)

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“…As we described previously, the Chicago C isolate was obtained after i.v. inoculation of a naive rabbit and harvesting of disseminated skin lesions (22) and has been used extensively in studies of TprK antigenic variation (15,17,18,(23)(24)(25). Because the Chicago C strain is known to have a high rate of tprK variation, special care was taken to ensure each inoculum was as isogenic at tprK as possible.…”

Section: Methodsmentioning

confidence: 99%

Antigenic Variation of TprK Facilitates Development of Secondary Syphilis

et al. 2014

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Although primary syphilis lesions heal spontaneously, the infection is chronic, with subsequent clinical stages. Healing of the primary chancre occurs as antibodies against outer membrane antigens facilitate opsonophagocytosis of the bacteria by activated macrophages. TprK is an outer membrane protein that undergoes antigenic variation at 7 variable regions, and variants are selected by immune pressure. We hypothesized that individual TprK variants escape immune clearance and seed new disseminated lesions to cause secondary syphilis. As in human syphilis, infected rabbits may develop disseminated secondary skin lesions. This study explores the nature of secondary syphilis, specifically, the contribution of antigenic variation to the development of secondary lesions. Our data from the rabbit model show that the odds of secondary lesions containing predominately TprK variant treponemes is 3.3 times higher than the odds of finding TprK variants in disseminated primary lesions (odds ratio [OR] ‫؍‬ 3.3 [95% confidence interval {CI}, 0.98 to 11.0]; P ‫؍‬ 0.055) and that 96% of TprK variant secondary lesions are likely seeded by single treponemes. Analysis of antibody responses demonstrates significantly higher antibody titers to tprK variable region sequences found in the inoculum compared to reactivity to tprK variant sequences found in newly arising secondary lesions. This suggests that tprK variants escape the initial immune response raised against the V regions expressed in the inoculum. These data further support a role for TprK in immune evasion and suggest that the ability of TprK variants to persist despite a robust immune response is instrumental in the development of later stages of syphilis.

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Section: Methodsmentioning

confidence: 99%

Antigenic Variation of TprK Facilitates Development of Secondary Syphilis

et al. 2014

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“…pertenue DNA. The analysis of the available T. pallidum and non-T. pallidum strain genomes (98,(110)(111)(112)114) confirmed that these methods could also be applied to detect nucleic acids from all of these treponemal strains, but without differentiating them. Examples of molecular tests include the amplification of the tmpA (TP0768) and the 4D genes (also known as tpf-1 [TP1038]), used by Hay et al (201,207) or the amplification of the bmp gene (TP1016) used by Noordhoek et al (202).…”

Section: Direct Detection Methodsmentioning

confidence: 81%

The Endemic Treponematoses

2014

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SUMMARY The agents of human treponematoses include four closely related members of the genus Treponema : three subspecies of Treponema pallidum plus Treponema carateum . T. pallidum subsp. pallidum causes venereal syphilis, while T. pallidum subsp. pertenue , T. pallidum subsp. endemicum , and T. carateum are the agents of the endemic treponematoses yaws, bejel (or endemic syphilis), and pinta, respectively. All human treponematoses share remarkable similarities in pathogenesis and clinical manifestations, consistent with the high genetic and antigenic relatedness of their etiological agents. Distinctive features have been identified in terms of age of acquisition, most common mode of transmission, and capacity for invasion of the central nervous system and fetus, although the accuracy of these purported differences is debated among investigators and no biological basis for these differences has been identified to date. In 2012, the World Health Organization (WHO) officially set a goal for yaws eradication by 2020. This challenging but potentially feasible endeavor is favored by the adoption of oral azithromycin for mass treatment and the currently focused distribution of yaws and endemic treponematoses and has revived global interest in these fascinating diseases and their causative agents.

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“…pertenue, Fribourg-Blanc, and T. paraluiscuniculi lysates (4,41,47,60). More recently, several comparative genomics studies confirmed the high level of relatedness among these treponemal strains (22,42,43,56).…”

mentioning

confidence: 73%

“…With the exception of the Nichols Gen, Dal-1, and Street14 strains, whose genome sequences are already available (GenBank accession numbers AE000520.1, CP000805.1, and CP003115.1, respectively), all other strains were propagated in our laboratory for sequencing purposes. The Chicago strain genome was previously obtained in our laboratory (22) (GenBank accession number CP001752.1). The Seattle Nichols strain was supplied by James N. Miller (University of California, Los Angeles, CA) in 1979; the Sea 81-4 strain was isolated in Seattle from a primary lesion in 1981; the Chicago strain was initially supplied by Paul Hardy and Ellen Nell (Johns Hopkins University, Baltimore, MD), along with the Cuniculi A, Samoa D, Iraq B, and Fribourg-Blanc strains.…”

Section: Methodsmentioning

confidence: 99%

Comparative Investigation of the Genomic Regions Involved in Antigenic Variation of the TprK Antigen among Treponemal Species, Subspecies, and Strains

et al. 2012

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bAlthough the three Treponema pallidum subspecies (T. pallidum subsp. pallidum, T. pallidum subsp. pertenue, and T. pallidum subsp. endemicum), Treponema paraluiscuniculi, and the unclassified Fribourg-Blanc treponeme cause clinically distinct diseases, these pathogens are genetically and antigenically highly related and are able to cause persistent infection. Recent evidence suggests that the putative surface-exposed variable antigen TprK plays an important role in both treponemal immune evasion and persistence. tprK heterogeneity is generated by nonreciprocal gene conversion between the tprK expression site and donor sites. Although each of the above-mentioned species and subspecies has a functional tprK antigenic variation system, it is still unclear why the level of expression and the rate at which tprK diversifies during infection can differ significantly among isolates. To identify genomic differences that might affect the generation and expression of TprK variants among these pathogens, we performed comparative sequence analysis of the donor sites, as well as the tprK expression sites, among eight T. pallidum subsp. pallidum isolates (Nichols Gen, Nichols Sea, Chicago, Sea81-4, Dal-1, Street14, UW104, and UW126), three T. pallidum subsp. pertenue isolates (Gauthier, CDC2, and Samoa D), one T. pallidum subsp. endemicum isolate (Iraq B), the unclassified FribourgBlanc isolate, and the Cuniculi A strain of T. paraluiscuniculi. Synteny and sequence conservation, as well as deletions and insertions, were found in the regions harboring the donor sites. These data suggest that the tprK recombination system is harbored within dynamic genomic regions and that genomic differences might be an important key to explain discrepancies in generation and expression of tprK variants among these Treponema isolates.

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Complete Genome Sequence and Annotation of the Treponema pallidum subsp. pallidum Chicago Strain

Cited by 54 publications

References 11 publications

Antigenic Variation of TprK Facilitates Development of Secondary Syphilis

Antigenic Variation of TprK Facilitates Development of Secondary Syphilis

The Endemic Treponematoses

Comparative Investigation of the Genomic Regions Involved in Antigenic Variation of the TprK Antigen among Treponemal Species, Subspecies, and Strains

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