Influence of acid on motility and chemotactic response of Helicobacter pylori in gastric mucin

Despite the highly acidic environment of the human stomach, Helicobacter pylori inhabits the gastric mucosa of half of the world population. While a fraction of the infected individuals develop gastric diseases, the presence of H. pylori has also been linked to benefits such as protection against allergies. The pathogenic and beneficial aspects of the bacteria require intricate balance in its motility, colonization and interaction with the host. In this dissertation I focus on understanding the factors that influence motility. The first part of this dissertation presents a comparison of the microrheology and the bacterial motility in healthy and tumor human gastric mucins. Active bacteria motion led to shear-thinning of the mucin solution and decreased its viscosity. The tumor mucin showed the lowest viscosity and its microrheology was most affected by bacterial motion. The second part of the dissertation elucidates the interplay between acidity and gastric mucin microrheology on motility. H. pylori motility shows a non-monotonic pH dependence, with the median of speed distribution peaking at pH4 in aqueous broth, below which the flagella motors fail due to high external proton concentration and bacteria become immotile below pH3. In contrast, in mucin the viscosity dominates motility; the median speed peaks at pH5 related to the approaching sol-gel transition around pH4. Additionally, the cell rotation increases monotonically with decreasing pH in mucin, implying that bacteria sense mechanical stress and increase rotation in an attempt to escape from mucin gel. The last part of the thesis examines chemotaxis of H. pylori in presence of a linear pH gradient in broth using single-channel microfluidics. The chemotaxis of H. pylori was most prominent at pH3-4.5; below pH3 the bacteria is immotile and above pH4.5 the bacteria resume random swimming directions. Individual, directed trajectories suggest that bacteria slow down upon reaching pH5. Lastly, a microfluidic assay was developed to explore the viscous fingering of gastric acid in mucin. With proper injection pressure, single acid channels can be created in mucin solutions. Microrheology analysis reveals that mucin gels and swells in the vicinity of the acid channel, which squeezes the acid in forming a thin finger pattern