Helicobacter pylori has been shown to require flagella for infection of the stomach. To analyze whether flagella themselves or motility is needed by these pathogens, we constructed flagellated nonmotile mutants. This was accomplished by using both an insertion mutant and an in-frame deletion of the motB gene. In vitro, these mutants retain flagella (Fla ⁺ ) but are nonmotile (Mot ⁻ ). By using FVB/N mice, we found that these mutants had reduced ability to infect mice in comparison to that of their isogenic wild-type counterparts. When these mutants were coinfected with wild type, we were unable to detect any motB mutant. Finally, by analyzing the 50% infectious dose, we found that motility is needed for initial colonization of the stomach mucosa. These results support a model in which motility is used for the initial colonization of the stomach and also to attain full infection levels.

Flagellar motility of Campylobacter jejuni and Helicobacter pylori influences host colonization by promoting migration through viscous milieus such as gastrointestinal mucus. This review explores mechanisms C. jejuni and H. pylori employ to control flagellar biosynthesis and chemotactic responses. These microbes tightly control the activities of σ⁵⁴ and σ²⁸ to mediate ordered flagellar gene expression. In addition to phase-variable and posttranslational mechanisms, flagellar biosynthesis is regulated spatially and numerically so that only a certain number of organelles are placed at polar sites. To mediate chemotaxis, C. jejuni and H. pylori combine basic chemotaxis signal transduction components with several accessory proteins. H. pylori is unusual in that it lacks a methylation-based adaptation system and produces multiple CheV coupling proteins. Chemoreceptors in these bacteria contain nonconserved ligand binding domains, with several chemoreceptors matched to environmental signals. Together, these mechanisms allow for swimming motility that is essential for colonization.

To characterize the mechanism by which receptors propagate conformational changes across membranes, nitroxide spin labels were attached at strategic positions in the bacterial aspartate receptor. By collecting the electron paramagnetic resonance spectra of these labeled receptors in the presence and absence of the ligand aspartate, ligand binding was shown to generate an ∼1 angstrom intrasubunit piston-type movement of one transmembrane helix downward relative to the other transmembrane helix. The receptor-associated phosphorylation cascade proteins CheA and CheW did not alter the ligand-induced movement. Because the piston movement is very small, the ability of receptors to produce large outcomes in response to stimuli is caused by the ability of the receptor-coupled enzymes to detect small changes in the conformation of the receptor.

SUMMARY: Despite decades of effort, Helicobacter pylori infections remain difficult to treat. Over half of the world's population is infected by H. pylori , which is a major cause of duodenal and gastric ulcers as well as gastric cancer. During chronic infection, H. pylori localizes within the gastric mucosal layer, including deep within invaginations called glands; thanks to its impressive ability to survive despite the harsh acidic environment, it can persist for the host's lifetime. This ability to survive and persist in the stomach is associated with urease production, chemotactic motility, and the ability to adapt to the fluctuating environment. Additionally, biofilm formation has recently been suggested to play a role in colonization. Biofilms are surface-associated communities of bacteria that are embedded in a hydrated matrix of extracellular polymeric substances. Biofilms pose a substantial health risk and are key contributors to many chronic and recurrent infections. This link between biofilm-associated bacteria and chronic infections likely results from an increased tolerance to conventional antibiotic treatments as well as immune system action. The role of this biofilm mode in antimicrobial treatment failure and H. pylori survival has yet to be determined. Furthermore, relatively little is known about the H. pylori biofilm structure or the genes associated with this mode of growth. In this review, therefore, we aim to highlight recent findings concerning H. pylori biofilms and the molecular mechanism of their formation. Additionally, we discuss the potential roles of biofilms in the failure of antibiotic treatment and in infection recurrence.

Helicobacter pylori is a human gastric pathogen associated with gastric and duodenal ulcers as well as specific gastric cancers. H. pylori infects approximately 50% of the world's population, and infections can persist throughout the lifetime of the host. Motility and chemotaxis have been shown to be important in the infection process of H. pylori . We sought to address the specific roles of chemotaxis in infection of a mouse model system. We found that mutants lacking cheW , cheA , or cheY are all nonchemotactic and infect FVB/N mice with an attenuated phenotype after 2 weeks of infection. If infections proceeded for 6 months, however, this attenuation disappeared. Histological and culture analysis revealed that nonchemotactic mutants were found only in the corpus of the stomach, while the wild type occupied both the corpus and the antrum. Further analysis showed that nonchemotactic H. pylori isolates had an increased 50% infectious dose and were greatly outcompeted when coinfected with the wild type. If nonchemotactic mutants were allowed to establish an infection, subsequent infection with the wild type partially displaced the nonchemotactic mutants, indicating a role for chemotaxis in maintenance of infection. The data presented here support four roles for chemotaxis in H. pylori mouse infections: (i) establishing infection, (ii) achieving high-level infection, (iii) maintaining an infection when there are competing H. pylori present, and (iv) colonizing all regions of the stomach.