Spirochetes

Spirochetes are gram-negative, motile, spiral bacteria, which can cause a number of serious diseases in humans including syphilis, yaws, Lyme disease, and relapsing fever. Spirochaeta, Treponema, Borrelia, and Leptospira are the examples of spirochetes genera.

A multi‑panel scientific figure illustrating structural domains of MOSP constructs and their incorporation into nanodiscs. At the top left is a cartoon ribbon diagram of the MOSPᶜ domain shown in green. Below it is a horizontal domain map spanning residues 1–543, with color‑coded segments: a short green N‑terminal region (1–20), a long blue segment labeled MOSPᴺ (113–348), and a red C‑terminal region labeled MOSPᶜ (364–542). To the right are two additional ribbon diagrams: one labeled MOSPᶜ, showing the C‑terminal β‑sheet fold, and a longer two‑domain structure labeled MOSPᴺ and MOSPᶜ stacked vertically. A full‑length model is labeled MOSPᴾᴸ. The lower half of the figure contains a grayscale cryo‑electron microscopy image of nanodisc particles, showing a field of roughly circular particles distributed across the grid. An inset in the upper right corner displays a class‑averaged top view of a trimeric particle. A scale bar of 100 nm appears in the lower right corner of the micrograph. Beneath the image, text reads “Trimeric MOSPᶜ in nanodiscs.”

Phylogenetic analysis, however, shows that treponemes form a single cluster separate from gram negative and positive bacteria, which is further corroborated with the findings of special types of glycolipid structures in outer membrane that differ significantly from other gram negative bacteria. We are particularly interested in T. pallidum, which is a treponema agent of syphilis, and T. denticola, which has been implicated as the cause of periodontal disease. The major outer sheath protein (MOSP) is a primary virulence determinant in T. denticola, it can also be considered as the parental ortholog for the T. pallidum repeat (Tpr) family of proteins in the syphilis spirochete. In collaboration with Dr. Radolf from Uconn Health, we are performing structural and functional characterization of MOSP and several associated proteins to better understand outer membrane biogenesis in T. denticola and in spirochetes in general.