Describe the relationship between helicobacter pylori virulence factors,host genetics and the environment that drives the disease outcome
Answers
Helicobacter pylori is a spiral-shaped Gram-negative bacterium that colonizes the human stomach and can establish a long-term infection of the gastric mucosa, a condition that affects the relative risk of developing various clinical disorders of the upper gastrointestinal tract, such as chronic gastritis, peptic ulcer disease, mucosa-associated lymphoid tissue (MALT) lymphoma, and gastric adenocarcinoma. H. pylori presents a high-level of genetic diversity, which can be an important factor in its adaptation to the host stomach and also for the clinical outcome of infection. There are important H. pylori virulence factors that, along with host characteristics and the external environment, have been associated with the different occurrences of diseases. This review is aimed to analyzing and summarizing the main of them and possible associations with the clinical outcome.
Keywords: Helicobacter pylori, virulence factors, chronic gastritis, peptic ulcer disease, gastric adenocarcinoma
Introduction
Helicobacter pylori is a flagellate Gram-negative spiral-shaped bacterium found on the luminal surface of the gastric epithelium. H. pylori organisms are 2.5–5.0 μm long and 0.5–1.0 μm wide, with four to six polar-sheated flagella, which are essential for bacterial motility.1
Infection is generally acquired during childhood and persists life-long in the absence of antibiotic treatment. Although the first isolation of the microorganism was in 1983 by Marshall and Warren,2 it has been demonstrated that H. pylori has a long period of co-evolution with humans, going back at least since human migration out of Africa about 60,000 years ago.3,4 This co-evolution is reflected on DNA sequence signatures observed in H. pylori strains of different geographic origins and has enabled the mapping of human migration out of Africa. This prolonged and intimate relationship is likely to have shaped the large and diverse repertoire of strategies that H. pylori employs to establish robust colonization and persist in the gastric niche.5,6
The routes of transmission of H. pylori still remain unclear. Person-to-person transmission and intrafamilial spread seem to be the main route, based on the intrafamilial clustering observed in some studies.7,8 Children are often infected by a strain, which is a genetic fingerprint identical to that of their parents, and they maintain this genotype even after moving to a different environment.9
The finding of strain-specific genes from the comparison of sequenced H. pylori strains demonstrates the high diversity of H. pylori genome,10 and this high level of genetic diversity can be an important factor in its adaptation to the host stomach and also for the clinical outcome of infection, an aspect that remains unclear. However, it is thought to involve an interplay among the virulence of infecting strains, host genetics, and environmental factors,11 and experience with other bacterial pathogens suggests that H. pylori-specific factors may influence the microorganism’s pathogenicity.
Since pathogen isolation, H. pylori infection has been associated with the development of various clinical disorders of the upper gastrointestinal tract, such as chronic gastritis, peptic ulcer disease, mucosa-associated lymphoid tissue (MALT) lymphoma, and gastric adenocarcinoma.12 In 1994, H. pylori was classified as a group I carcinogen by The International Agency for Research on Cancer and was regarded as a primary factor for gastric cancer (GC) development.13 In addition, during the last years, H. pylori infection has also been associated with some extra-digestive diseases, such as iron-deficiency anemia,14 idiopathic thrombocytopenic purpura (ITP),15,16 cardiovascular diseases,17,18 hepatobiliary diseases,19,20 and diabetes mellitus,21,22 among others.
As regard to the host, the genetic factors have a significant impact on the clinical outcome and anatomical distribution of H.