Sphingolipids associate with the chlamydial nucleoid and mark developmental transitions in Chlamydia trachomatis
Abstract
Chlamydia trachomatis is an obligate intracellular bacterial pathogen and a leading cause of sexually transmitted infections worldwide. During its biphasic developmental cycle, infectious, non-replicative elementary bodies alternate with replicative reticulate bodies within a membrane-bound intracellular niche known as the inclusion. C. trachomatis relies heavily on host-derived metabolites, including sphingolipids, which are essential for inclusion integrity, bacterial growth and production of infectious progeny. Here, using expansion microscopy, we uncover an unexpected localization of sphingolipid derivatives within the highly condensed DNA nucleoids of elementary bodies. These sphingolipids are released from nucleoids prior to DNA decondensation during the elementary-to-reticulate body transition, the earliest phenotypic event in the complex developmental cycle of these bacteria. Thereafter, nucleoids undergo a characteristic DNA decondensation process that we visualized by expansion microscopy. By combining super-resolution imaging with a FRET-based metabolic tracking approach and lipidomics, we identified sphingomyelin derived from the sphingolipid analogues as the sphingolipid species predominantly associated with the condensing nucleoids of elementary bodies. Notably, reticulate bodies arrested in their developmental stage fail to accumulate sphingomyelin, suggesting a potential role for this lipid in stage-specific DNA condensation.
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BibTeX
@article{ruhling2026sphingolipids,
title = {{Sphingolipids associate with the chlamydial nucleoid and mark developmental transitions in Chlamydia trachomatis}},
author = {Marcel Rühling and Fabienne Wagner and Till Epprecht and Paul F. Köhling and Fabian Schumacher and Stefan Sachs and Louise Kersting and Julian Fink and Lina Girndt and Burkhard Kleuser and Markus Sauer and Jürgen Seibel and Gregor L. Weiss and Thomas Rudel},
journal = {Nature Communications},
year = {2026},
month = sep,
doi = {10.1038/s41467-026-77974-3},
url = {https://www.nature.com/articles/s41467-026-77974-3},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Sphingolipids associate with the chlamydial nucleoid and mark developmental transitions in Chlamydia trachomatis
AU - Marcel Rühling
AU - Fabienne Wagner
AU - Till Epprecht
AU - Paul F. Köhling
AU - Fabian Schumacher
AU - Stefan Sachs
AU - Louise Kersting
AU - Julian Fink
AU - Lina Girndt
AU - Burkhard Kleuser
AU - Markus Sauer
AU - Jürgen Seibel
AU - Gregor L. Weiss
AU - Thomas Rudel
PY - 2026
DA - 2026/09/30
JO - Nature Communications
DO - 10.1038/s41467-026-77974-3
UR - https://www.nature.com/articles/s41467-026-77974-3
AB - Chlamydia trachomatis is an obligate intracellular bacterial pathogen and a leading cause of sexually transmitted infections worldwide. During its biphasic developmental cycle, infectious, non-replicative elementary bodies alternate with replicative reticulate bodies within a membrane-bound intracellular niche known as the inclusion. C. trachomatis relies heavily on host-derived metabolites, including sphingolipids, which are essential for inclusion integrity, bacterial growth and production of infectious progeny. Here, using expansion microscopy, we uncover an unexpected localization of sphingolipid derivatives within the highly condensed DNA nucleoids of elementary bodies. These sphingolipids are released from nucleoids prior to DNA decondensation during the elementary-to-reticulate body transition, the earliest phenotypic event in the complex developmental cycle of these bacteria. Thereafter, nucleoids undergo a characteristic DNA decondensation process that we visualized by expansion microscopy. By combining super-resolution imaging with a FRET-based metabolic tracking approach and lipidomics, we identified sphingomyelin derived from the sphingolipid analogues as the sphingolipid species predominantly associated with the condensing nucleoids of elementary bodies. Notably, reticulate bodies arrested in their developmental stage fail to accumulate sphingomyelin, suggesting a potential role for this lipid in stage-specific DNA condensation.
SN - 2041-1723
ER -