Abstract
The swimming motility of Vibrio cholerae is a virulence factor that aids in breaching the mucus layer of the small intestine. V. cholerae cells have a curved cell shape and previous work demonstrated that loss of curvature decreases infectivity. Here we investigate the mechanism by which V. cholerae's curvature affects single-cell motility within mucus-mimicking environments. Using a multiscale chemotaxis assay, we compared the chemotactic performance of wild-type curved cells (O1 El Tor C6706) and straight mutants under linear chemical gradients in liquid solutions, viscous solutions, and soft agar hydrogels. Our findings reveal that curved and straight V. cholerae exhibit similar swimming properties in liquid and purely viscous solutions but significantly differ in hydrogels, with curved cells demonstrating an 86% increase in average chemotactic drift compared to straight mutants in the same chemical gradients. Trajectory analysis indicates that swimming speeds are comparable, but straight mutants experience more frequent stalls, reducing the total time spent swimming. We also found that stalls further reduce chemotactic performances by imposing an average reorientation of bacteria down the chemical gradient, regardless of cell shape. In-silico coarse-grained molecular dynamics simulations corroborate these results and extend them over the wide range of intestinal mucus hydrogel stiffnesses. This model also identifies an optimal curvature for enhanced movement through hydrogel-like meshes that is close to the real median curvature of the pathogen. Our findings thus highlight the mechanisms underpinning cell shape's role in V. cholerae's pathogenicity and underscore the necessity of studying bacterial behaviors under conditions that simulate host environments.