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Infiltration to infection: key virulence players of Helicobacter pylori pathogenicity

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Abstract

Purpose

This study aims to comprehensively review the multifaceted factors underlying the successful colonization and infection process of Helicobacter pylori (H. pylori), a prominent Gram-negative pathogen in humans. The focus is on elucidating the functions, mechanisms, genetic regulation, and potential cross-interactions of these elements.

Methods

Employing a literature review approach, this study examines the intricate interactions between H. pylori and its host. It delves into virulence factors like VacA, CagA, DupA, Urease, along with phase variable genes, such as babA, babC, hopZ, etc., giving insights about the bacterial perspective of the infection The association of these factors with the infection has also been added in the form of statistical data via Funnel and Forest plots, citing the potential of the virulence and also adding an aspect of geographical biasness to the virulence factors. The biochemical characteristics and clinical relevance of these factors and their effects on host cells are individually examined, both comprehensively and statistically.

Results

H. pylori is a Gram-negative, spiral bacterium that successfully colonises the stomach of more than half of the world's population, causing peptic ulcers, gastric cancer, MALT lymphoma, and other gastro-duodenal disorders. The clinical outcomes of H. pylori infection are influenced by a complex interplay between virulence factors and phase variable genes produced by the infecting strain and the host genetic background. A meta-analysis of the prevalence of all the major virulence factors has also been appended.

Conclusion

This study illuminates the diverse elements contributing to H. pylori's colonization and infection. The interplay between virulence factors, phase variable genes, and host genetics determines the outcome of the infection. Despite biochemical insights into many factors, their comprehensive regulation remains an understudied area. By offering a panoramic view of these factors and their functions, this study enhances understanding of the bacterium’s perspective, i.e. H. pylori's journey from infiltration to successful establishment within the host's stomach.

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Data availability

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Abbreviations

H. pylori :

Helicobacter pylori

OMPs:

Outer Membrane proteins

OMVs:

Outer Membrane Vesicles

T4SS:

Type IV secretion system

Bab:

Blood group antigen-binding adhesins

Sab:

Sialic acid-binding adhesins

Oip:

Outer inflammatory protein

CagPAI:

Cag pathogenicity island

VacA:

Vacuolating cytotoxin A

IL:

Interleukin

ROS:

Reactive Oxygen Species

dupA:

Duodenal Ulcer Promoting Gene A

iceA:

Induced by Contact with Epithelium Gene A

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Acknowledgements

The authors express their deep gratitude to the Science & Engineering Research Board (SERB) Government of India for the financial assistance (Grant no. SRG/2019/000457) to OM & AB.

Funding

Science & Engineering Research Board (SERB) Government of India for the financial assistance (Grant no. SRG/2019/000457) to OM & AB.

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AB: Writing–original draft, review and editing. OSS: Writing–review, meta-analysis and figure preparation. AS: Writing–review. SB: Data curation, Formal Analysis, Idea development. RC: Formal analysis and review; SK: Statistical analysis; OM: Formal analysis, Idea development, Manuscript preparation and Manuscript revision.All the authors read and approved the final review draft.

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Correspondence to Oindrilla Mukherjee.

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Bhattacharjee, A., Sahoo, O.S., Sarkar, A. et al. Infiltration to infection: key virulence players of Helicobacter pylori pathogenicity. Infection 52, 345–384 (2024). https://doi.org/10.1007/s15010-023-02159-9

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