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Infection and Immunity, March 2006, p. 1896-1906, Vol. 74, No. 3
0019-9567/06/$08.00+0     doi:10.1128/IAI.74.3.1896-1906.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

TprK Sequence Diversity Accumulates during Infection of Rabbits with Treponema pallidum subsp. pallidum Nichols Strain{dagger}

Rebecca E. LaFond,1* Arturo Centurion-Lara,1,2 Charmie Godornes,2 Wesley C. Van Voorhis,1,2 and Sheila A. Lukehart1,2

Departments of Pathobiology,1 Medicine, University of Washington, Seattle, Washington2

Received 16 September 2005/ Returned for modification 28 November 2005/ Accepted 21 December 2005

The tprK gene in Treponema pallidum undergoes antigenic variation. In all T. pallidum isolates examined to date, except the Nichols type strain, heterogeneous tprK sequences have been identified. This heterogeneity is localized to seven variable (V) regions, and tprK sequence diversity accumulates with serial passage in naïve rabbits. The T. pallidum Nichols genome described a single tprK sequence, and after decades of independent passage, only minor tprK sequence diversity is seen among the Nichols strains from different laboratories. We hypothesized that T. pallidum Nichols is capable of only limited tprK diversification. To address this hypothesis, we passaged the T. pallidum Nichols strain in naïve rabbits at the peak of infection (rapid passage) or after the adaptive immune response had cleared most organisms in vivo (slow passage). After 22 rapid passages (9- to 10-day intervals), no tprK V region sequence changes were observed. In contrast, after two slow passages (30- to 35-day intervals), three V regions had sequences that were completely different from that of the original inoculum. New sequences were observed in all seven V regions by the fifth slow passage. In contrast to the rapid-passaged Nichols strain, rapid-passaged Chicago C, a clonal strain isolated from the highly diverse parent Chicago strain, developed significant tprK diversification. These findings suggest that tprK variation can occur, but at a lower rate, in Nichols and that immune pressure may be required for accumulation of bacteria with diverse tprK sequences. Adaptation to growth in rabbits may explain the limited repertoire of V region sequences seen in the Nichols strain.

* Corresponding author. Mailing address: Department of Pathobiology, Box 359779, Harborview Medical Center, 325 Ninth Ave., Seattle, WA 98104. Phone: (206) 341-5360. Fax: (206) 341-5363. E-mail: rlafond{at}u.washington.edu.

{dagger} Supplemental material for this article may be found at http://iai.asm.org/.

Editor: A. D. O'Brien

Infection and Immunity, March 2006, p. 1896-1906, Vol. 74, No. 3
0019-9567/06/$08.00+0     doi:10.1128/IAI.74.3.1896-1906.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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