Proteomic analysis of the Treponema pallidum subsp. pallidum SS14 strain: coverage and comparison with the Nichols strain proteome

Front Microbiol. 2024 Dec 11:15:1505893. doi: 10.3389/fmicb.2024.1505893. eCollection 2024.

Abstract

Introduction: Strains of the syphilis spirochete, Treponema pallidum ssp. pallidum, group into one of two deep-branching clades: the Nichols clade or the globally dominant Street Strain 14 (SS14) clade. To date, in-depth proteome-wide analyses have focused on Nichols clade strains.

Methods: The T. pallidum SS14 clade reference strain (SS14) proteome was characterized via protein detection and quantification analyses using mass spectrometry, and comparison was made to the Nichols clade reference strain (Nichols) proteome.

Results: Approximately two thirds of all proteins from T. pallidum SS14 were detected and quantitated, allowing confirmation of expression of 259 proteins for the first time in this strain, including 11 known/putative outer membrane proteins (OMPs). SS14 and Nichols proteome comparative analyses demonstrated similar protein expression/quantification profiles between the two strains, and showed that inter-strain amino acid sequence differences are located primarily within predicted surface-exposed regions in 16 known/putative OMPs.

Discussion: This study provides the first comparative analyses of the proteomes from the T. pallidum SS14 and Nichols strains. The findings inform syphilis vaccine design by confirming the expression of known/predicted OMP vaccine candidates in SS14 treponemes, and via the finding that most inter-strain variable residues found in OMPs are predicted to be located in surface-exposed, host-facing regions of these proteins.

Keywords: Treponema pallidum; outer membrane proteins; proteomics; syphilis; vaccine candidates.

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This work was supported by grants R37AI051334, U19AI144133 and U01AI182035 (CEC) from the National Institute of Allergy and Infectious Diseases (NIAID) at the National Institutes of Health (NIH), as well as an award from Open Philanthropy (52345).