Helicobacter pylori infection: An overview of bacterial virulence factors and pathogenesis - PubMed (original) (raw)

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Helicobacter pylori infection: An overview of bacterial virulence factors and pathogenesis

Cheng-Yen Kao et al. Biomed J. 2016 Feb.

Abstract

Helicobacter pylori pathogenesis and disease outcomes are mediated by a complex interplay between bacterial virulence factors, host, and environmental factors. After H. pylori enters the host stomach, four steps are critical for bacteria to establish successful colonization, persistent infection, and disease pathogenesis: (1) Survival in the acidic stomach; (2) movement toward epithelium cells by flagella-mediated motility; (3) attachment to host cells by adhesins/receptors interaction; (4) causing tissue damage by toxin release. Over the past 20 years, the understanding of H. pylori pathogenesis has been improved by studies focusing on the host and bacterial factors through epidemiology researches and molecular mechanism investigations. These include studies identifying the roles of novel virulence factors and their association with different disease outcomes, especially the bacterial adhesins, cag pathogenicity island, and vacuolating cytotoxin. Recently, the development of large-scale screening methods, including proteomic, and transcriptomic tools, has been used to determine the complex gene regulatory networks in H. pylori. In addition, a more available complete genomic database of H. pylori strains isolated from patients with different gastrointestinal diseases worldwide is helpful to characterize this bacterium. This review highlights the key findings of H. pylori virulence factors reported over the past 20 years.

Keywords: Gastric cancer; Helicobacter pylori; Pathogenesis; Virulence factor.

Copyright © 2016 Chang Gung University. Published by Elsevier B.V. All rights reserved.

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Figures

Fig. 1

Fig. 1

Schematic diagram of Helicobacter pylori infection and pathogenesis. The urease activity and flagella-mediated motility of H. pylori facilitate its survival and movement toward the lower mucus gel above the epithelium, followed by several adhesins, including blood-antigen binding protein A, sialic acid-binding adhesin, and other outer membrane proteins interacting with receptors on the host epithelium cells. After successful colonization, toxins, including cytotoxin-associated gene A, and vacuolating cytotoxin A, are involved in damage of host tissue and intracellular replication.

Fig. 2

Fig. 2

Current model of the flagellar transcriptional regulatory cascade for Helicobacter pylori flagellar biosynthesis. These genes are color-coded on the basis of their classification in the transcriptional regulatory cascade: black (class 1 genes), gray (class 2 genes), and purple (class 3 genes). Class 1 flagellar genes comprise most of the major regulatory genes of the flagellar system, including σ54 (RpoN), and FlgR. Formation of the flagellar T3SS has been proposed to create a signal detected by the FlgS sensor kinase, resulting in autophosphorylation of the protein. Phosphotransfer to the FlgR response regulator activates the protein, allowing for interactions with and stimulation of σ54. The expression of σ54 is positively regulated by CsrA through unclear mechanism. Alternative sigma factor σ28 (FliA) and structural proteins, including the minor flagellin FlaB, belong to Class 2 flagellar genes and are under the control of σ54. The T3SS facilitates the ordered secretion of the class 2 rod, ring, and hook proteins. The class 3 genes include flaA, which encodes the major flagellin, and those for other minor filament proteins, under the control of σ28.

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