ORIGINAL RESEARCH article
Front. Immunol.
Sec. Microbial Immunology
Treponema pallidum TprD and TprK Are Adhesins and Their Surface Expression Promotes Spirochetal Opsonophagocytosis
1. New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, United States
2. University of Washington, Seattle, United States
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Abstract
ABSTRACT Background: Treponema pallidum subspecies pallidum causes systemic syphilis, exclusively infects humans in nature and can persist for decades in the absence of treatment despite generating robust adaptive immune responses. The T. pallidum repeat (Tpr) family of outer membrane proteins are immunogenic and are implicated in immune evasion, indicating them to be virulence factors displayed on the spirochete surface. Long-term survival of T. pallidum is largely attributed to sparse surface-exposed outer membrane proteins and antigenic variation in the major surface protein TprK through phase variation. This mechanism has been studied for decades; however, the functions of Tprs of this extracellular pathogen are not yet experimentally determined. Methods: In this study, the localization and functional roles of TprD and TprK were investigated using a heterologous spirochete expression system and a gain-of-function approach by employing a noninfectious, non-adherent Borrelia burgdorferi B314 strain. Opsonophagocytosis of engineered B. burgdorferi as well as of T. pallidum Nichols and SS14 strains was evaluated using J774A.1 macrophages and mouse antibodies raised against predicted surface-exposed loops of TprD and TprK using IncuCyte system. Results: Both TprD and TprK were found to be surface exposed in engineered B. burgdorferi and infectious T. pallidum strains. Expression of these proteins conferred adherence to several mammalian cell lines in vitro. In addition, antibodies we generated recognized TprD and TprK on the surface of spirochetes and significantly enhanced macrophage-mediated opsonophagocytosis. Conclusion: Our findings here demonstrate that TprD and TprK function as T. pallidum adhesins that are also targets of opsonic antibodies. These Tprs likely facilitate tissue colonization during infection, while also rendering the pathogen susceptible to immune clearance. Our findings support inclusion of TprD and TprK as components of a multivalent vaccine against syphilis.
Summary
Keywords
adherence, opsonophagocytosis, Syphilis, TPRD, TprK, Treponema pallidum
Received
08 January 2026
Accepted
18 February 2026
Copyright
© 2026 Zafar, Azuama, Xu, Giacani and Parveen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Nikhat Parveen
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