Paumet Research

G. Cingolani, M. McCauley, A. Lobley, A. Bryer, J. Wesolowski, R. Lokareddy, E. Ronzone, J. Perilla, F. Paumet “An intramolecular clamp controls the fusogenic activity of a chlamydial SNARE-like protein”, Nature Communications (2019) 10: 2747 https://www.nature.com/articles/s41467-019-10806-9

This study presents the atomic structure of the cytoplasmic domain of IncA, which reveals a non-canonical four-helix bundle. Structure-based mutagenesis, molecular dynamics simulation, and functional cellular assays identify an intramolecular clamp that is essential for IncA-mediated homotypic membrane fusion during infection.

T. Monteiro-Bras, J. Wesolowski, F. Paumet “Depletion of SNAP-23 and Syntaxin4 alters lipid droplet homeostasis during Chlamydia infection”, Microbial Cell (2019) 7:46-58. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6993123/

This study demonstrates that the loss of SNAP23 and Syntaxin4 results in the dysregulation of Chlamydia-induced lipid droplets, indicating that both of these SNAREs play a critical role in lipid droplet homeostasis during Chlamydia infection. Ultimately, our data highlights the importance of lipid droplets and their regulation in Chlamydia development.

J. Wesolowski, MM. Weber, A. Nawrotek, CA. Dooley, M. Calderon, CM. St. Croix, T. Hackstadt, J. Cherfils, F. Paumet (2017) “Chlamydia Hijacks ARF GTPases To Coordinate Microtubule Posttranslational Modifications and Golgi Complex Positioning” mBio 8: e02280-16

This study provides the first evidence that a chlamydial protein CT813 recruits the GTPases ARF1 and ARF4, which in turn play a critical role in controlling post-translationally modified microtubules around the inclusion. Furthermore, this study demonstrates that Chlamydia trachomatis hijacks this novel function of ARF to reposition the Golgi mini stacks during infection.

E. Ronzone, J Wesolowski, Laura D. Bauler, Anshul Bhardwaj, Ted Hackstadt, F. Paumet (2014) “An alpha-helical core encodes the dual functions of the chlamydial protein IncA” Journal of Biological Chemistry, 289

Here, the functional core of the SNARE-like protein IncA has been identified, which provides the basis for a more comprehensive understanding of its mechanisms of action and could aid in the development of novel therapeutics capable of interfering with its pathogenic function in vivo. This project provides the most detailed understanding of how a chlamydial inclusion protein operates to manipulate membrane fusion.

J. Wesolowski, F. Paumet (2014) “Escherichia coli exposure inhibits exocytic SNARE-mediated membrane fusion in mast cells” Traffic 15:516-530

This study demonstrates that E. coli exposure inhibits the formation of the exocytic SNARE complex and thus the release of granules. As a result, IgE-induced inflammatory reactions are significantly dampened. Ultimately, these results suggest that the microenvironment within which mast cells reside modulates their activation.