Introduction

H. pylori infections are among the major causes of peptic ulcers and gastric cancers. The development of robust inflammation in response to these flagellated, motile bacteria is correlated with poor prognosis. Chemotaxis plays a crucial role in the colonization by H. pylori, enabling the bacteria to swim toward favorable chemical environments. However, the biophysical mechanisms by which H. pylori migrate toward and colonize favorable niches in the stomach are not understood. We are determining how the chemotaxis signaling network in this species influences the motility pattern in single cells at a mechanistic level. These investigations are critical in developing innovative therapeutics to eradicate this opportunistic pathogen.

This study is funded by NIH R01-GM141690

Methods

We perform chemotaxis and motility assays with a phase microscope fitted with an automated micropipette. The micropipette delivers a tiny amount of stimulant or ligand in a reservoir containing swimming H. pylori cells. The response of individual cells to the point source of the ligand is recorded in the form of digital videos. Next, we use particle-tracking algorithms to quantify single-cell trajectories in response to the chemical. Quantifying cell trajectories allows us to measure the changes in the chemotaxis signaling dynamics in each cell. 

Results

We measured cell responses to two chemoeffectors: 1mM Urea(attractant) and 50mM HCl (repellent). We observed that individual cells increased their probability of swimming close to underlying surfaces in response to urea. Near-surface swimming trapped the cells in specific regions for significant durations (~few minutes) due to hydrodynamic interactions with the surface. However, in the case of HCl, the migratory pattern was markedly different with limited or no hydrodynamic trapping. Whereas H. pylori accumulated near the urea source, they actively avoided HCl.

Conclusion

The canonical chemotaxis framework predicts that H. pylori cells will exhibit multiple errors during biased migration. Also, H. pylori lack key chemotaxis enzymes found in E. coli, without which sensitive detection of ligands with a wide dynamic is not possible. Despite this, H. pylori exhibit robust capabilities of migrating toward urea-rich sources and away from HCl sources. Our findings that certain chemicals trap the swimming cells near bounding surfaces to promote accumulation are shedding light on potential directions for future research. Understanding the intricacies of biased migration in H. pylori could offer valuable insights into how these cancer-causing microbes breach the immune barriers in the stomach.