Loss of helical cell shape alters Helicobacter pylori's swimming behavior in a viscous solution of gastric mucin

Helicobacter pylori colonizes the stomach of ~50% of all humans. Helical cell shape is thought to enhance H. pylori’s flagellar-based motility and to enable bacteria to move through the highly viscous mucus layer via a corkscrew mechanism, allowing efficient colonization of the stomach. In support of this theory, deletion of cell shape-determining genes (csd) results in distinct non-helical shapes (curved, “c”-shaped, “s”-shaped, and straight rod), and cell-shape mutants show stomach colonization defects in a mouse model of infection. We tested the migration of H. pylori in soft agar; “c”-shaped and straight rod mutants show measurable attenuation suggesting that cell shape impacts motility. We developed a live-cell imaging assay to automatically track hundreds of individual bacteria in purified gastric mucin, the relevant polymer for H. pylori in the stomach. Wild-type bacteria show a wide range of swimming velocities both within individual tracks and between bacteria. Analysis of the distribution of maximal velocities for wild-type bacteria revealed one peak at 5-15 µm/sec and a second broader peak from 20-50 µm/sec. In contrast, two straight rod mutants (csd4 and csd6) showed a single maximal velocity peak at 5-20 µm/sec. These results suggest H. pylori displays multiple swimming modes and helical cell shape contributes the high-velocity mode. We also quantified reversals in swimming direction but reversal frequency does not underlie the velocity differences observed. Additional experiments with other cell-shape mutants and exploring other aspects of swimming behavior will provide new insights into how cell-body shape affects H. pylori motility in the gastric mucosa.