Biology subjects

Schnupf, P.

Publications and source records attributed to Schnupf, P..

3 recordsLinked to original sources

bioRxiv2025

Segmented filamentous bacteria undergo a structural transition at their adhesive tip during unicellular to filament development

Segmented filamentous bacteria (SFB) are intestinal commensals that promote immune system development and pathogen protection through intimate attachment to the ileal epithelium. Attachment occurs via the tip of unicellular teardrop-shaped SFB, called intracellular offsprings (IOs), before outgrowth into filaments. To characterize this critical stage of the SFB life-cycle, we imaged SFB using cryo-electron microscopy and tomography. IOs were surrounded by a repetitive surface (S)-layer that became replaced by disordered hair-like structures uniquely at the tip. Upon outgrowth into filaments, the S-layer was exchanged for a morphologically distinct repetitive hair- like layer. The bacterial structures and morphological transition were conserved across SFB from mouse and rat origin, while growth of mouse-SFB under non-attachment conditions in a heterologous host affected the SFB tip length and relative proportion of the tip stages. Moreover, the filament tip displayed surface exposure of the major Th17 antigen, a ubiquitous cell wall protein, underscoring the unique properties of the adhesive tip. This study identifies a novel IO- specific S-layer and reveals a conserved developmental transition of the SFB tip surface including the transient appearance of structures consistent in location and timing with being involved in host cell attachment.

microbiology↗

bioRxiv2025

Characterization and description of Clostridium filamentum ETTB, a novel gut bacterium with TLR5 modulating properties

The Clostridium genus is highly heterogeneous, encompassing numerous species and strains, many of which remain to be isolated and characterized to better understand their relationship to host physiology. This study aimed to isolate and characterize novel bacterial species within the Clostridium genus and explore their potential links to host health. Under microaerophilic conditions, we isolated and characterized three bacterial isolates belonging to a new anaerobic Clostridium species, designating Clostridium sp. DSM 115107 (Clostridium filamentum ETTB3) as the type strain. C. filamentum ETTB isolates are rod- to filament-shaped, Gram-positive bacteria and exhibit poor growth when cultured on rich media such as LYBHI. Genome sequencing and phylogenetic analysis revealed that C. filamentum ETTB belongs to the Clostridium genus and clusters closely with Clostridium saudiense JCC. Interestingly, C. filamentum ETTB has a significantly smaller genome compared to C. saudiense JCC containing a reduced repertoire of genes involved in carbohydrate degradation and amino acid synthesis and a larger number of genes related to cell motility, including an additional copy of the fliC gene. Unlike C. saudiense, C. filamentum ETTB adopted a filamentous morphology when in contact with Caco-2 cells and stimulate the TLR5 pathway in Caco-2 cells. Metagenomics analysis revealed that C. filamentum ETTB is present in both industrialized and non-industrialized populations, although the relative abundance varying considerably between and within individuals. Our study identifies a novel bacterial strain adapted for the human gut that has the potential to influence host immune response by activating TLR5 pathway.

microbiology↗

bioRxiv2022

Diet prevents the expansion of segmented filamentous bacteria and ileo-colonic inflammation in a model of Crohn's disease

Crohns disease (CD) is associated with changes in the microbiota, and murine models of CD-like ileo-colonic inflammation depend on the presence of microbial triggers. Increased abundance of unknown Clostridiales and the microscopic detection of filamentous structures close to the epithelium of Tnf {Delta}ARE mice pointed towards segmented filamentous bacteria (SFB), a commensal well-known to induce the maturation of Th17 cell-derived immune responses that is highly implicated in the pathogenesis of IBD. We show that the abundance of SFB strongly correlates with the severity of CD-like ileal inflammation in Tnf {Delta}ARE and SAMP/Yit mice. SFB mono-colonization of germ-free Tnf {Delta}ARE mice confirmed the causal link and resulted in severe ileo-colonic inflammation, characterized by elevated tissue levels of Tnf and Il-17, neutrophil infiltration and loss of Paneth and goblet cell function. Co-colonization of SFB in human-microbiota associated Tnf {Delta}ARE mice confirmed that SFB presence is indispensable for disease development. Screening of 412 ileal and colonic mucosal biopsies from IBD patients using previously published and newly designed human SFB-specific primer sets showed no presence of SFB in human tissue samples. Simulating the protective effect of exclusive enteral nutrition (EEN) by feeding SFB mono-colonized Tnf {Delta}ARE mice EEN-like purified diet antagonized SFB colonization and prevented disease development in Tnf {Delta}ARE mice, clearly demonstrating the important role of diet in modulating this IBD-related but murine pathobiont.

microbiology↗