The Tprk Protein of Treponema pallidum Is Periplasmic and Is Not a Target of Opsonic Antibody or Protective Immunity

doi:10.1084/jem.193.9.1015

Published online 7 May 2001.

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© The Rockefeller University Press, 0022-1007/2001/5/1015/ $5.00
The Journal of Experimental Medicine, Volume 193, Number 9, May 7, 2001 1015-1026

Original Article

The Tprk Protein of Treponema pallidum Is Periplasmic and Is Not a Target of Opsonic Antibody or Protective Immunity

Karsten R.O. Hazlett^a, Timothy J. Sellati^a, Tung T. Nguyen^a, David L. Cox^d, Michael L. Clawson^a, Melissa J. Caimano^a, and Justin D. Radolf^a^,b^,c

^a Center for Microbial Pathogenesis, University of Connecticut Health Center, Farmington, Connecticut 06030
^b Department of Genetics and Developmental Biology, University of Connecticut Health Center, Farmington, Connecticut 06030
^c Department of Medicine, University of Connecticut Health Center, Farmington, Connecticut 06030
^d Division of STD Laboratory Research, Centers for Disease Control and Prevention, Atlanta, Georgia 30333
Center for Microbial Pathogenesis, University of Connecticut Health Center, 263 Farmington Ave., Farmington, CT 06030-3710.860-679-8130860-679-8129

jradolf{at}up.uchc.edu

The finding that Treponema pallidum, the syphilis spirochete,contains 12 orthologs of the Treponema denticola outer membranemajor sheath protein has engendered speculation that membersof this T. pallidum repeat (Tpr) family may be similarly surfaceexposed. In this regard, the TprK protein was reported to bea target of opsonic antibody and protective immunity and subjectto immunologically driven sequence variation. Despite thesefindings, results from our previous analyses of treponemal outermembranes in concert with computer-based predictions for TprKprompted us to examine the cellular location of this protein.TprK–alkaline phosphatase fusions expressed in Escherichiacoli demonstrate that TprK contains a signal peptide. However,opsonophagocytosis assays failed to indicate surface exposureof TprK. Moreover, results from three independent methodologies,i.e., (a) indirect immunofluorescence analysis of agarose-encapsulatedorganisms, (b) proteinase K treatment of intact spirochetes,and (c) Triton X-114 phase partitioning of T. pallidum conclusivelydemonstrated that native TprK is entirely periplasmic. Consistentwith this location, immunization with the recombinant proteinfailed to induce either protective immunity or select for TprKvariants in the rabbit model of experimental syphilis. Thesefindings challenge the notion that TprK will be a componentof an efficacious syphilis vaccine.

Key Words: spirochete • membrane protein • vaccine • antigenic variation • opsonization

T.J. Sellati's present address is Center for Immunology andMicrobial Disease, Albany Medical College, 47 New Scotland Ave.,Albany, NY 12208-3479.

Abbreviations used in this paper: GlpQ, glycerophosphodiesterphospho-diesterase; IRS, immune rabbit sera; LRT, likelihoodratio test; Msp, major sheath protein; NRS, normal rabbit sera;OM, outer membrane; PK, proteinase K; PP, periplasmic/periplasm;RIT, rabbit infectivity test; RT, reverse transcription; TpEf,endoflagella; Tpr, Treponema pallidum repeat.

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