Authors
Fajardo-Ruiz, E., Kring, E., Schum, D., Brameyer, S., Kretschmer, R., Wang, T., Hesse, J., Gantner, I., Weissert, E., Goebner, L., Milles, L., Gulder, T., Sieber, S., Jung, K.
Abstract
Glucocorticoids such as dexamethasone (DXE) are first-line treatments for inflammatory bowel disease (IBD). IBD patients also experience an increased colonization of the intestine by sulfate-reducing Desulfovibrio spp. Here, we show that DXE modulates bacterial motility in the gut commensal Desulfovibrio desulfuricans through a metabolism-independent mechanism. To identify bacterial targets, we developed a DXE-derived chemical probe and performed affinity-based protein profiling, which revealed the flagellar cap protein FliD (Ddes_0530) as a principal binding partner. Structural modeling using AlphaFold3 and Boltz2 predicted DXE binding within a conserved groove of the FliD C-terminal domain. Furthermore, the tip of the flagellum of Desulfovibrio, but not that of Escherichia coli could be fluorescently labeled with TAMRA-DXE, but not with TAMRA-norethiosterone, suggesting specific binding of DXE to Ddes_0530 in situ. As consequence of this interaction, transmission electron microscopy showed that DXE treatment prevented flagellation in a subpopulation and reduced flagellar length in D. desulfuricans strains ATCC 27774 and CCUG 72978, respectively. Quantitative motility tracking revealed a non-monotonic, dose-dependent modulation of swimming velocity, with peak stimulation at 10 M DXE, accompanied by straighter trajectories and enhanced net displacement. Together, these findings uncover a previously unrecognized mode of action for DXE which directly perturbs flagellar biogenesis and motility of an important gut microbiome member of IBD patients.
Preprint server:
bioRxiv
The authors list and abstract were imported from bioRxiv on 08 Jul 2026.
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