A human epithelial co-culture system reveals distinct host cell interaction behaviours for Treponema pallidum
5 affiliations
- 1Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK
- 2Department of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC Australia
- 3Department of Medicine, Division of Allergy and Infectious Diseases, University of Washington, Seattle, WA USA
- 4Department of Global Health, University of Washington, Seattle, WA USA
- 5London School of Hygiene & Tropical Medicine, London, UK
Abstract
Treponema pallidum subsp. pallidum, the causative agent of syphilis, remains difficult to study owing to long-standing limitations in in vitro cultivation. Although a rabbit epithelial cell co-culture system (Sf1Ep) enabled major advances, the absence of human cell-based models limits clinical relevance and mechanistic understanding of host–pathogen interactions. Here, we established a co-culture system using human epithelial cell lines capable of supporting T. pallidum growth in vitro. Six epithelial or epithelial-like cell lines from diverse tissues were evaluated under microaerophilic conditions using standard cultivation medium. CAL-39 (vulva) and HepG2 (liver) supported T. pallidum survival, replication, characteristic growth behaviours, and long-term passage at levels comparable to Sf1Ep cells. Growth kinetics, attachment dynamics, and motility were quantified over extended culture. Using live-cell imaging, we defined two distinct host-cell interaction behaviours: surface-associated crawling and stable single-polar attachment. Both behaviours were observed across all tested cell lines but persisted only in those permissive for sustained growth. Together, our findings establish clinically relevant human epithelial co-culture models for T. pallidum, provide new insights into host-cell-dependent growth and motility, and create a platform for mechanistic studies of syphilis pathogenesis and vaccine target discovery.
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BibTeX
@article{capuccini2026human,
title = {{A human epithelial co-culture system reveals distinct host cell interaction behaviours for Treponema pallidum}},
author = {Katia Capuccini and Divenita Govender and David Goulding and Cecilia Kyanya and Shivani Pasricha and Lorenzo Giacani and Nicholas R. Thomson and Linda Grillová},
journal = {Communications Biology},
year = {2026},
month = jul,
doi = {10.1038/s42003-026-10635-9},
url = {https://doi.org/10.1038/s42003-026-10635-9},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - A human epithelial co-culture system reveals distinct host cell interaction behaviours for Treponema pallidum
AU - Katia Capuccini
AU - Divenita Govender
AU - David Goulding
AU - Cecilia Kyanya
AU - Shivani Pasricha
AU - Lorenzo Giacani
AU - Nicholas R. Thomson
AU - Linda Grillová
PY - 2026
DA - 2026/07/07
JO - Communications Biology
DO - 10.1038/s42003-026-10635-9
UR - https://doi.org/10.1038/s42003-026-10635-9
AB - Treponema pallidum subsp. pallidum, the causative agent of syphilis, remains difficult to study owing to long-standing limitations in in vitro cultivation. Although a rabbit epithelial cell co-culture system (Sf1Ep) enabled major advances, the absence of human cell-based models limits clinical relevance and mechanistic understanding of host–pathogen interactions. Here, we established a co-culture system using human epithelial cell lines capable of supporting T. pallidum growth in vitro. Six epithelial or epithelial-like cell lines from diverse tissues were evaluated under microaerophilic conditions using standard cultivation medium. CAL-39 (vulva) and HepG2 (liver) supported T. pallidum survival, replication, characteristic growth behaviours, and long-term passage at levels comparable to Sf1Ep cells. Growth kinetics, attachment dynamics, and motility were quantified over extended culture. Using live-cell imaging, we defined two distinct host-cell interaction behaviours: surface-associated crawling and stable single-polar attachment. Both behaviours were observed across all tested cell lines but persisted only in those permissive for sustained growth. Together, our findings establish clinically relevant human epithelial co-culture models for T. pallidum, provide new insights into host-cell-dependent growth and motility, and create a platform for mechanistic studies of syphilis pathogenesis and vaccine target discovery.
SN - 2399-3642
ER -