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Ganguillet, S.

Publications and source records attributed to Ganguillet, S..

3 recordsLinked to original sources

Emergent spatial structure in the gut microbiota is driven by bacterial growth and gut contractions

Spatial structure can determine function and evolution of bacterial communities. The gut microbiota is known to be spatially structured longitudinally along the many meters of the gastrointestinal tract, but micro-scale structure in the gut lumen has not been extensively explored. In samples from mice and humans, we show that upper large-intestinal content behaves as a non-Newtonian fluid that changes its viscoelastic properties under the force of gut contractions. This phenomenon is sufficient to explain micro-scale bacterial clustering in the murine cecum, resulting from growth within the gel-like structure of cecum content, and periodic disruption due to peristalsis-driven shear-thinning and clearance. Shear-thinning can also explain the surprising observation that fed beads enter the tip of the mouse cecum by flow along the epithelial cell layer before being mixed into the cecum content. Our study shows mechanistically how spatial structure in the gut emerges through the interplay of microbial and host physiology and highlights the possibility of host control over gut microbiota distribution via gut contractions. One sentence summaryWe show how spatial structure emerges in the gut microbiota through bacterial growth in the matrix of gut content.

systems biology↗

Surface crosslinking of virus-like particles increases resistance to proteases, low pH and mechanical stress for mucosal applications

AbstractVirus-like particles (VLPs) are emerging as nano-scaffolds in a variety of biomedical applications including the delivery of vaccine antigens to mucosal surfaces. These soft, colloidal, and proteinaceous structures (capsids) are nevertheless susceptible to mucosal environmental factors which limit their usefulness. We addressed this issue by crosslinking multiple capsid surface reactive residues using polyethylene glycol tethers. Surface crosslinking enhanced the colloidal stability and mechanical strength of VLPs against low pH, proteases, and mechanical agitation, while it did not interfere with function as vaccine. Chemical crosslinking thus offers a viable means to enhance the resilience of VLPs in mucosal applications.

biophysics↗

Gasdermin D is the only Gasdermin that provides non-redundant protection against acute Salmonella gut infection

Gasdermins (GSDMs) share a common functional domain structure and are best known for their capacity to form membrane pores. These pores are hallmarks of a specific form of cell death called pyroptosis and mediate the secretion of pro-inflammatory cytokines such as interleukin 1{beta} (IL1{beta}) and interleukin 18 (IL18). Thereby, Gasdermins have been implicated in various immune responses against cancer and infectious diseases such as acute Salmonella Typhimurium (S.Tm) gut infection. However, to date, we lack a comprehensive functional assessment of the different Gasdermins (GSDMA-E) during S.Tm infection in vivo. Here, we have performed littermate-controlled oral S.Tm infections to investigate the impact of all murine Gasdermins. While GSDMA, -C and -E appear dispensable, we show that GSDMD (i) restricts S.Tm loads in the gut tissue and systemic organs, (ii) controls gut inflammation kinetics, and (iii) prevents epithelium disruption by 72h of the infection. Full protection requires GSDMD expression by both bone-marrow-derived lamina propria cells and intestinal epithelial cells (IECs). In vivo experiments, 3D- and 2D-enteroid infections further show that infected IEC extrusion proceeds also without GSDMD, but that GSDMD controls the permeabilization and morphology of the extruding cells and affects extrusion kinetics. As such, this work identifies a non-redundant multipronged role of GSDMD in mucosal tissue defence against a common enteric pathogen. HIGHLIGHTSO_LIGasdermin D restricts Salmonella Typhimurium (S.Tm) translocation across the gut tissue, controls gut inflammation kinetics, and prevents epithelium disruption by 72h of the infection. C_LIO_LIGasdermins A, C and E appear dispensable for protection against acute S.Tm gut infection. C_LIO_LIGasdermin D in bone-marrow-derived lamina propria cells and intestinal epithelial cells complement each other to suppress gut tissue S.Tm loads. C_LIO_LIGasdermin D is not required for extrusion of infected intestinal epithelial cells but drives their permeabilization and affects qualitative features of the extrusion process. C_LI

immunology↗