Biophysical Society Thematic Meeting | Ascona 2026

Mechanobiology of Infection

Poster Abstracts

17-POS Board 17 MUCOSAL SURFACES INFLUENCE KLEBSIELLA PNEUMONIAE

PATHOGENICITY IN THE GUT AND LUNG Miro Thorsten Wilhelm Plum ; Alexandre Persat EPFL, Institute of Bioengineering and Global Health Institute, School of Life Science, Lausanne, Switzerland Klebsiella pneumoniae (KP) is an opportunistic pathogen responsible for pneumonia, systemic infections, and abscess formation. Although commonly found as a commensal in the gastrointestinal tract, KP can disseminate and cause severe infections, particularly in the lung. A major virulence factor is its polysaccharide capsule, which promotes immune evasion by inhibiting phagocytosis and complement-mediated killing. Hypervirulent KP strains (hvKP), characterized by an enlarged capsule, exhibit enhanced invasive potential and are increasingly associated with severe infections. The global emergence of hvKP, alongside rising antibiotic resistance, poses a significant public health threat. Despite this, the mechanisms by which hvKP causes lung disease while remaining commensal in the gut remain poorly understood. To investigate tissue-specific virulence and commensalism, we used live-cell microscopy to visualize fluorescently labeled KP on mucus-secreting human lung and gut organoids. KP grows into filaments to form discrete clusters on top of the epithelium. hvKP forms clusters approximately larger than non-capsulated strains. In lung organoids, hvKP clusters required 30 h to invade tissue, while mucus removal reduced this to 20 h. Fitting to this observation, in colonic organoids, a thicker and more hydrated mucus layer blocked KP from establishing tissue contact even after 40 h, but its removal restored invasion to lung-like levels, thereby showing that mucus is a strong regulator of infection dynamics. Once reaching the epithelium, hvKP formed large (~300 µm) clusters that caused localized tissue damage. Time-lapse imaging showed hvKP growing between cell junctions which lead to slow compression and subsequent lysis of the host cells, whereas non-capsulated strains did not invade tissue under the same conditions. These findings highlight that KP directly colonizes and invades lung tissue, while thicker, more hydrated mucus in the gut promotes bacterial colonization within the mucus layer, preventing tissue invasion.

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