# Functional assessment of TprC/D and TprK proteins of syphilis causing spirochete, Treponema pallidum

> **NIH NIH R21** · RUTGERS BIOMEDICAL AND HEALTH SCIENCES · 2022 · $235,500

## Abstract

SCIENTIFIC ABSTRACT
Syphilis has an estimated global prevalence of 36M cases, with more than 11M new infections occurring
per year around the world. In the United States alone, the number of cases of infectious syphilis has steadily
increased since 2000, indicating that this disease is still a public health concern, particularly considering that it
can lead to serious neurological and cardiovascular sequelae. Understanding the biological function of the outer
membrane proteins (OMPs) of the syphilis agent, Treponema pallidum subsp. pallidum (T. pallidum), is one of
the greatest challenges in the study of syphilis pathogenesis. Progress towards functional characterization of
OMPs is hindered by the lack of an independent, pure culture system for T. pallidum, genetic intractability of the
pathogen, the need to use of rabbits for bacterial propagation, the paucity of OMPs in T. pallidum outer
membrane, and the fragility of this cellular compartment. Despite so many limitations, undertaking the study of
T. pallidum OMPs can greatly enhance our understanding of the role of these virulence factors in syphilis
pathogenesis and even provide important clues on new approaches to successfully control syphilis, such as by
developing a protective vaccine. Twelve of putative OMPs/virulence factors belong to the T. pallidum repeat
(Tpr) family, which are a group of highly immunogenic proteins predicted to be homologous to the Treponema
denticola (T. denticola) major sheath protein (Msp), a surface virulence factor with porin and adhesin properties.
Limited or no experimental evidence is available until now regarding functions of various Tprs. Based on
homology to Msp, structural models for the Tprs and our preliminary data, we hypothesize that several Tprs
also have dual roles as adhesins and porin transporters. T. pallidum and Borrelia burgdorferi, which causes
Lyme disease, are physiologically and structurally related spirochetes. Unlike T. pallidum, B. burgdorferi can be
genetically manipulated and transformed to express selected Tprs as if they were constituents of its OM. The
validity of the surrogate system to study Tprs is supported by our preliminary data showing that when TprD2 and
TprK are expressed on the surface of a non-infectious and poorly adherent B. burgdorferi strain, these proteins
enhance adhesion to Glioma and epithelial cells and facilitate amino acids and peptides uptake. Here, we plan
to further test our hypothesis and establish function of these important virulence factors by using both our well-
tried B. burgdorferi, as well as the T. denticola msp mutant surrogate systems. We will conduct following studies
to test our hypothesis: (1) Determine whether T. pallidum TprC, D2, and K proteins mediate attachment to host
cells in differential manner by recognizing the specific host receptors/ECM components on each cell type, and
(2) Determine the role of T. pallidum TprC, D2, and K proteins as channels involved in nutrient transport.
Signifi...

## Key facts

- **NIH application ID:** 10477191
- **Project number:** 7R21AI151336-02
- **Recipient organization:** RUTGERS BIOMEDICAL AND HEALTH SCIENCES
- **Principal Investigator:** Nikhat Parveen
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $235,500
- **Award type:** 7
- **Project period:** 2021-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10477191

## Citation

> US National Institutes of Health, RePORTER application 10477191, Functional assessment of TprC/D and TprK proteins of syphilis causing spirochete, Treponema pallidum (7R21AI151336-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10477191. Licensed CC0.

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