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Antigenic variation of TprK V regions abrogates specific antibody binding in syphilis.

ABSTRACT: The tprK gene in the syphilis spirochete, Treponema pallidum subsp. pallidum, undergoes antigenic variation in seven variable (V) regions. tprK is highly variable within T. pallidum strains, and a method has been developed to derive clones of T. pallidum that express a single, unique tprK sequence. Rabbits were infected with three different T. pallidum clones or the parent strain from which the clones were derived, and their sera were examined by immunoassay for antibody reactivity against synthetic peptides representing the TprK V regions from each clone. The parent strain expresses many different V region sequences, and infection with this strain induced antibody responses against a wide variety of V regions. In rabbits infected with the Chicago C clone, antibodies developed against all of the V regions except V1, while antibodies developed against only V5, V6, and V7 in Chicago A-infected rabbits. During Chicago B infection, antibodies developed against all of the V regions except V1 and V3. Antibodies were highly specific for the V regions of the infecting clone, and cross-reactivity was rare. The demonstration that the V regions elicit a variant-specific antibody response supports the hypothesis that TprK variants may help organisms to avoid the developing immune response in infected individuals, contributing to the ability of T. pallidum to establish chronic infection.

SUBMITTER: LaFond RE

PROVIDER: S-EPMC1695500 | biostudies-literature | 2006 Nov

REPOSITORIES: biostudies-literature

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Antigenic variation of TprK V regions abrogates specific antibody binding in syphilis.

LaFond Rebecca E RE Molini Barbara J BJ Van Voorhis Wesley C WC Lukehart Sheila A SA

Infection and immunity 20060821 11

The tprK gene in the syphilis spirochete, Treponema pallidum subsp. pallidum, undergoes antigenic variation in seven variable (V) regions. tprK is highly variable within T. pallidum strains, and a method has been developed to derive clones of T. pallidum that express a single, unique tprK sequence. Rabbits were infected with three different T. pallidum clones or the parent strain from which the clones were derived, and their sera were examined by immunoassay for antibody reactivity against synth ...[more]

PMID: 16923793

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Project description:TprK antigenic variation is acknowledged as an important strategy developed by Treponema pallidum to achieve immune evasion. Previous studies applied short-read sequencing to explore tprK gene sequence diversity in clinical samples; however, due to the limitations of short-read sequencing, it was difficult to determine the linkage between the seven V regions, and crucial information about full-length tprK variants was lost. Although two recent studies explored complete tprK gene profiles in natural human syphilis infection, there are still too few profiled full-length tprK variants among clinical T. pallidum isolates to fully understand the characteristics of TprK coding diversity. Here, Pacific Biosciences (PacBio) long-read sequencing was applied to examine the diversity of full-length tprK variants in 21 clinical T. pallidum isolates from 11 patients with primary syphilis and 10 patients with secondary syphilis. A total of 398 high-confidence full-length sequences, which presented remarkable sequence heterogeneity, were found. However, these full-length tprK variants exhibited limited variation in length and GC content, showing 24 length types and average GC content of 51.5 ± 0.42% and 51.6 ± 0.26% for primary and secondary syphilis samples, respectively. Additionally, the combined patterns of mutated V regions generating new tprK variants were obviously different in primary and secondary syphilis samples. The diversity of tprK gene sequences in primary syphilis samples may represent the underlying variability of the bacterium; conversely, the variability of the tprK gene in secondary syphilis samples may more accurately reflect how T. pallidum escapes host immune clearance. These data highlight the tprK gene as an important coding gene that shows conflicting genetic characteristics but underlies the persistence of spirochete infection. IMPORTANCE The resurgence of syphilis in both low- and high-income countries has attracted attention, and persistent infection by the pathogen has long been a research focus. The tprK gene, encoding the hypervariable outer membrane protein, is thought to be responsible for pathogen immune evasion and persistent infection. Here, PacBio long-read sequencing was applied to examine the diversity of full-length tprK variants in 21 clinical T. pallidum isolates from 11 patients with primary syphilis and 10 patients with secondary syphilis. The results showed that the sequences of the tprK gene were remarkably heterogeneous; however, the sequences presented limited variation in length and GC content. The investigation of the combined patterns of the V regions allowed us to gain insight into the features of the tprK gene generating new variants at different clinical stages. The findings of this study will be helpful for further exploration of the pathogenesis of syphilis.

Dataset Information

Antigenic variation of TprK V regions abrogates specific antibody binding in syphilis.

Publications

Antigenic variation of TprK V regions abrogates specific antibody binding in syphilis.

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