Mélanie Foulon
University of Geneva, Switzerland
Shedding light on mycobacterial cell envelope dynamics
The mycobacterial cell envelope is a highly complex and dynamic structure that plays central roles in intracellular adaptation, immune modulation, and pathogenesis. Yet, how this lipid-rich surface is remodeled during infection, and how such remodeling influences host responses, remains poorly understood. In this seminar, I will present recent work showing that mycobacteria rapidly shed outer-envelope material during the earliest stages of intracellular infection. Using Mycobacterium marinum infection models combined with quantitative imaging, bacterial surface labeling, and single-cell approaches, we find that this shed material traffics through host endocytic compartments, disseminates to neighboring bystander cells, and alters their response to infection. I will show that exposure to shed mycobacterial material triggers a distinct response in these bystander cells, including damage-associated responses, transient changes in cell-cycle progression, and increased resistance to subsequent infection. These observations identify surface shedding as an early and conserved feature of intracellular mycobacterial infection, and suggest that envelope remodeling can influence host-pathogen interactions well beyond the infected cell itself. More broadly, this work supports a view of the mycobacterial cell envelope as a dynamic interface whose remodeling can shape both bacterial adaptation and the heterogeneity of host responses. I will discuss how these findings connect to broader questions about mycobacterial envelope biology, intracellular compartmentalization, and early host resistance mechanisms during infection.
Selected references
- D’Amico D., Raykov L., Soldati T. & Foulon M. (2025) Mycobacterial surface shedding drives bystander cells response during early intracellular infection. bioRxiv https://doi.org/10.1101/2025.11.13.687818
- Foulon M., Hüttel S.V., Breitsprecher L., Gauda W., Raykov L., Koliwer-Brandl H., Ohlhagen M., Thünauer R., Schwudke D., Hilbi H., Soldati T. & Barisch C. (2026) Intracellular compartmentalization shapes lipid access and metabolic fitness of mycobacteria. bioRxiv https://doi.org/10.64898/2026.02.10.704997
- Foulon M., et al. (2026) The orphan receptor GPR84 drives inflammation in Buruli ulcer development. Sci Transl Med 18(845):eads8681