Biology subjects

Goussard, S.

Publications and source records attributed to Goussard, S..

4 recordsLinked to original sources

bioRxiv2026

Apical adhesion of meningococci controls host cell basal traction force through Ancreopodia formation

Extracellular bacterial pathogens remodel the apical surface of host cells, but whether these local interactions are mechanically transmitted across the cell to the basal extracellular matrix remains unclear. Using a combination of in vitro infection models, high-resolution imaging, traction force microscopy and bacterial genetics, we show that Neisseria meningitidis (Nm) adhesion to endothelial cells triggers a rapid increase in traction forces and localized, colony-associated traction-force hotspots on the extracellular matrix. Formation of these hotspots is associated with a novel actin-rich structure, which we term ancreopodia, that links apical bacterial colonies to the basal substrate. Super-resolution microscopy revealed ancreopodia spanning the cell thickness, connecting apical cortical plaques to reorganized basal stress fibers and focal-adhesion components. Dynamic imaging demonstrated coordinated movements of bacterial colonies and basal mechanosensitive proteins, while analysis of pili mutants showed that pilus retraction is required to focus traction forces beneath colonies. Disruption of branched actin assembly or myosin-II activity likewise impaired apico-basal organization and vinculin recruitment. Functionally, Nm infection enhanced local anchoring while restricting single-cell migration and collective endothelial dynamics. Together, these findings identify ancreopodia as a vertical mechanotransduction structure through which an extracellular pathogen couples apical adhesion to basal force transmission and reshapes host-cell mechanics.

cell biology↗

bioRxiv2024

Bacterial growth under confinement requires transcriptional adaptation to resist metabolite-induced turgor pressure build-up

Bacterial proliferation often occurs in confined spaces, during biofilm formation, within host cells, or in specific niches during infection, creating mechanical constraints. We investigated how spatial confinement and growth-induced mechanical pressure affect bacterial physiology. Here, we found that, when proliferating in a confining microfluidic-based device with access to nutrients, Escherichia coli cells generate forces in the hundreds of kPa range. This pressure decouples growth and division, producing shorter bacteria with higher protein concentrations. This leads to cytoplasmic crowding, which ultimately arrests division and stalls protein synthesis. In this arrested state, the pressure produced by bacteria keeps increasing. A minimal theoretical model of bacterial growth predicts this novel regime of steady pressure increase in the absence of protein production, that we named overpressurization. In this regime, the Rcs pathway is activated and that abnormal shapes appear in rcs mutant populations only when they reach the overpressurized state. A uropathogenic strain of E. coli displayed the same confined growth phenotypes in vitro and requirement for Rcs in a mice model of urinary tract infection, suggesting that these pressurized regimes are relevant to understand the physiopathology of bacterial infections.

microbiology↗

bioRxiv2024

Infection-on-Chip: an in vitro human vessel to study Neisseria meningitidis colonization and vascular damages

Systemic infections leading to sepsis are life-threatening conditions that remain difficult to treat, and the limitations of current experimental models hamper the development of innovative therapies. Animal models are constrained by species-specific differences, while 2D cell culture systems fail to capture the complex pathophysiology of infection. To overcome these limitations, we developed a laser photoablation-generated, three-dimensional microfluidic model of meningococcal vascular colonization, a human-specific bacterium that causes sepsis and meningitis. Laser photoablation-generated hydrogel engineering allows the reproduction of vascular networks that are major infection target sites, and this model provides the relevant microenvironment reproducing the physiological endothelial integrity and permeability in vitro. By comparing with a human-skin xenograft mouse model, we show that the model system not only replicates in vivo key features of the infection, but also enables quantitative assessment with a higher spatiotemporal resolution of bacterial microcolony growth, endothelial cytoskeleton rearrangement, vascular E-selectin expression, and neutrophil response upon infection. Our device thus provides a robust solution bridging the gap between animal and 2D cellular models, paving the way for a better understanding of disease progression and developing innovative therapeutics.

synthetic biology↗

bioRxiv2018

Adhesion to nanofibers drives cell membrane remodeling through 1D wetting

The shape of cellular membranes is highly regulated by a set of conserved mechanisms. These mechanisms can be manipulated by bacterial pathogens to infect cells. Human endothelial cell plasma membrane remodeling by the bacterium Neisseria meningitidis is thought to be essential during the blood phase of meningococcal infection, but the underlying mechanisms are unknown. Here we show that plasma membrane remodeling occurs independently of F-actin, along meningococcal type IV pili fibers, by a novel physical mechanism we term \" onedimensional\" membrane wetting. We provide a theoretical model that gives the physical basis of 1D wetting and show that this mechanism occurs in model membranes interacting with model nanofibers, and in human cells interacting with model extracellular matrices. It is thus a new general principle driving the interaction of cells with their environment at the nanoscale that is diverted by meningococcus during infection.

cell biology↗