Anita Sumali

Background: Helicobacter pylori (H. pylori) is one of the most prevalent human pathogens worldwide, infecting approximately half of the global population¹. Its association with numerous gastrointestinal disorders, including gastritis, peptic ulcers, and gastric cancer highlights the urgent need for a thorough understanding of its pathogenesis mechanisms². While extensive research has shed light on its virulence factors and host interactions, a number of H. pylori pathogenesis aspects still remain incomplete.

Methods: The PubMed database was used in an online search from 2018-2024 using the keywords: “H. pylori pathogenesis”, “Bacterial Virulence”, “Bacterial Motility”, and “Antibiotic Resistance”.

Results: Studies showed that H. pylori is the first formally recognized bacterial carcinogen, with its virulence factors, including cytotoxin-associated gene A (CagA) and vacuolating cytotoxin A (VacA), contributing to disruption of host cellular processes and promoting inflammation, subsequently contributing to the instigation and progression of gastric malignancies ^{3, 4}. The bacterium’s ability to establish persistent colonization in the hostile gastric environment is facilitated by its remarkable adaptability, aided by factors such as urease production, flagellar motility, and the ability to modulate its surface properties ^{5, 6}. Host genetic susceptibility, environmental factors (such as diet and socioeconomic status), and microbial interactions within the gastric microbiota further influence the outcomes of H. pylori infection, highlighting the multifaceted nature of disease progression⁷.

Conclusions: Understanding the intricate interplay between the noted factors is essential for deciphering H. pylori pathogenesis and developing effective strategies for the prevention and treatment of H. pylori-associated diseases. For future therapies, targeting H. pylori chemotactic proteins as a therapeutic option may present as a promising strategy for treatment as opposed to using broad based antibiotics. For example, inhibition of chemotactic signaling pathways, which could inhibit the bacteria from responding to chemical gradients, as well as inhibiting flagellar proteins, which would inhibit movement of the bacteria thus inhibiting colonization. While these potential therapy options would not eliminate the bacteria itself from the GI tract, infection may be reduced by inhibiting the colonization process itself. It is worthwhile to target individuals who are most at risk for gastric cancer by looking at host, environmental, and bacterial risk factors. Epidemiology studies have shown that individuals on high sodium diets or have iron deficiency are at higher risk of gastric cancer. Smoking also increases risk of gastric cancer ⁸. While these areas for improvement have been identified, they haven’t been thoroughly explored, so this is something to hopefully be targeted in the near future.

Works Cited:

1. Kusters JG, van Vliet AHM, Kuipers EJ. (2006). Pathogenesis of Helicobacter pylori Infection. Clinical Microbiology Reviews, 19(3), 449– doi: 10.1128/CMR.00054-05
2. Qin Z, Lin W, Zhu S, Franco AT, Liu J. 2017. Imaging the Motility and Chemotaxis Machineries in Helicobacter pylori by Cryo-Electron Tomography. J Bacteriol 199:10.1128/jb.00695-16.
3. Stefano K, Marco M, Federica G, et al. (2018). Helicobacter pylori, transmission routes and recurrence of infection: state of the art. Acta Biomed, 89(Suppl 8), 72– doi: 10.23750/abm.v89i8-S.7947
4. Antani JD, Sumali AX, Lele TP, Lele PP. (2021). Asymmetric random walks reveal that the chemotaxis network modulates flagellar rotational bias in Helicobacter pylori. eLife, 10, e63936. doi: 10.7554/eLife.63936
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7. Lina TT, Alzahrani S, Gonzalez J, Pinchuk IV, Beswick EJ, Reyes VE. Immune evasion strategies used by Helicobacter pylori. World J Gastroenterol. 2014 Sep 28;20(36):12753-66. doi: 10.3748/wjg.v20.i36.12753. PMID: 25278676; PMCID: PMC4177461.
8. Brown LM. Helicobacter pylori: epidemiology and routes of transmission. Epidemiol Rev. 2000;22(2):283-97. doi: 10.1093/oxfordjournals.epirev.a018040. PMID: 11218379.