LecB from Pseudomonas aeruginosa modulates Piezo1 currents and localization in a time-dependent manner.

Infections with the Gram-negative opportunistic pathogen Pseudomonas aeruginosa are becoming increasingly difficult to treat due to growing antibiotic resistance. Complications often include disturbed wound healing and impaired cell migration of various cell types, including epithelial and immune cells in the host tissue. One bacterial virulence factor responsible for these effects is the carbohydrate-binding lectin LecB. It mediates adhesion to host cells, alters various cellular signaling pathways and internalizes several receptors, i.e. integrins. However, the full effects and mechanisms of how LecB influences the processes in the host cells are still largely unknown. In this study, we introduce a new host cell interaction partner of LecB with strong physiological impact. Using immunofluorescence and pull-down studies, we were able to show that LecB can interact with the cation nonselective stretch-activated channel Piezo1, which is expressed in various cell types. Recording Piezo1 currents with the patch-clamp technique in the in presence of LecB, we observed altered responses of Piezo1 to mechanical forces. After 30 min of LecB incubation time, mechanically-induced Piezo1 currents were higher compared to control, while after 3 h they were greatly reduced. Computational modeling suggests protein-protein and protein-carbohydrate interactions between LecB and Piezo1. This hypothesis is supported by inhibiting LecB-induced current changes by L-fucose or a LecB binding site mutant. From a more general perspective, our results highlight ion channels and their glycosylations as targets for bacterial lectins, improving our understanding of host-pathogen interactions and the evolution of bacterial infections, and hopefully providing the basis for the development of new therapeutics to combat antibiotic-resistant pathogens.