Biology subjects

Grassl, G. A.

Publications and source records attributed to Grassl, G. A..

3 recordsLinked to original sources

bioRxiv2026

Resilience of multispecies biofilm communities: Comparative analysis of a Veillonella dispar-dominant oral biofilm under diverse oxygen conditions in vitro

Oral multispecies biofilms developing on dental implants drive peri-implant mucositis and peri-implantitis. They are shaped by the physicochemical conditions of their surrounding environment, among which oxygen availability is an important influential factor. However, while oxygen tension fluctuates significantly within the peri-implant pocket, whether these environmental shifts are sufficient to influence the structure and composition of an established microbial community remains unclear. For this purpose, we evaluated the structure and composition of a four-species oral biofilm model comprising the species Streptococcus oralis, Actinomyces naeslundii, Veillonella dispar and Porphyromonas gingivalis, which was cultivated under normoxic (21% O2), hypoxic (1% O2) and anoxic (0% O2;) conditions for a period of 21 days. Biofilm 3D architecture, volume and membrane integrity was analyzed by LIVE/DEAD staining combined with confocal laser scanning microscopy. Community composition was assessed by quantitative real-time PCR and complemented by Fluorescence In Situ Hybridization (FISH) to provide structural context. While normoxia transiently promoted higher early biofilm volume and membrane integrity, the community exhibited remarkable long-term resilience, consistently maintaining a V. dispar-dominated structure across all oxygen gradients. Crucially, the obligate anaerobic pathogen P. gingivalis persisted as a viable minority (~1%) even under 21-day normoxic cultivation, sheltered within the deeper layers of the biofilm. These results suggest that clinical oxygen levels alone are not able to drastically modulate established oral biofilm communities and that oxygen-sensitive pathogens persist in a subclinical sanctuary protected by the surrounding non-pathogenic species.

microbiology↗

bioRxiv2026

Activated macrophages restrict invasive bacterial infection in a human intestinal organoid co-culture model

Intestinal organoids provide physiologically relevant models of the epithelial barrier, but lack the immune compartment that critically shapes host responses to infection. Here, we established a human colon organoid-derived monolayer co-culture system with macrophage-like THP-1 cells positioned directly beneath the epithelial layer. The model enabled controlled apical infection with Listeria monocytogenes and Salmonella Typhimurium while preserving epithelial barrier integrity. PMA-differentiated THP-1 cells reduced intracellular L. monocytogenes burden, whereas additional activation with IFN-{gamma} and LPS resulted in a pronounced reduction of both L. monocytogenes and S. Typhimurium, accompanied by decreased infection-associated cytotoxicity. Bulk RNA sequencing revealed a distinct co-culture transcriptional signature characterized by coordinated changes in inflammatory, antimicrobial, and epithelial lineage-associated programs. These included reduced HLA-D/MHC class II-associated gene expression, altered S100A8/S100A9 expression, and changes in epithelial lineage markers indicating a shift in epithelial cellular composition and differentiation state. Together, these findings establish a versatile human organoid-macrophage platform for dissecting epithelial-immune interactions and macrophage-associated control of invasive bacterial infection.

immunology↗

bioRxiv2019

Flagella methylation promotes bacterial adhesion and host cell invasion

The flagellum is the motility device of many bacteria and the long external filament is made of several thousand copies of a single protein, flagellin. While posttranslational modifications of flagellin are common among bacterial pathogens, the role of lysine methylation remained unknown. Here, we show that both flagellins of Salmonella enterica, FliC and FljB, are methylated at surface-exposed lysine residues. A Salmonella mutant deficient in flagellin methylation was outcompeted for gut colonization in a gastroenteritis mouse model. In support, methylation of flagellin promoted invasion of epithelial cells in vitro. Lysine methylation increased the surface hydrophobicity of flagellin and enhanced flagella-dependent adhesion of Salmonella to phosphatidylcholine vesicles and epithelial cells. In summary, posttranslational flagellin methylation constitutes a novel mechanism how flagellated bacteria facilitate adhesion to hydrophobic host cell surfaces and thereby contributes to efficient gut colonization and successful infection of the host.

microbiology↗