from Lyudmila Boyanova writing in Helicobacter pylori:

H. pylori infection outcomes strongly depend on the strain virulence. H. pylori displays enormous genetic diversity by frequent mutations, intra- or intergenomic recombinations and natural transformation, and additional phase variations by slipped-strand mispairing. H. pylori spiral shape, urease, motility, lipopolysaccharide (LPS) and outer membrane adhesins enable the establishment of the infection. H. pylori genetic diversity and induced immunomodulation contribute to the infection chronicity. Prevalence of virulence factors varies according to the patient disease, ethnicity, age and country. H. pylori VacA causes vacuolation, pore formation, disruption of endo-lysosomal activity, apoptosis in gastric cells and immunomodulation. CagA oncoprotein alters cell-signalling pathways and induces morphological changes, chromosomal instability, cell proliferation and apoptosis, interleukin (IL)-8 release and proto-oncogene activation. CagA type D EPIYA and increased number of C repeats has been linked to increased SHP-2 phosphatase activity and hence high risk for gastric cancer. In East Asia, nearly all strains have been highly virulent, carrying intact cagPAI, East Asian CagA and vacA s1/i1/m1 type, which can help to explain the high gastric cancer incidence there. Although the infection outcomes have shown strong association with cagA, cagPAI and vacA status of the strains, mainly in Western countries, the combined activity of all H. pylori virulence factors, involving also dupA, oipA, iceA, homB, babA, sabA, hopQ and other genes/gene status appears to be crucial for the infection pathogenesis. Tipα protein, HP-NAP, heat-shock-proteins, LPS mimicry and interaction with toll-like receptors influence the infection course as well. By the complex and well-coordinated interplay of its virulence factors, H. pylori adapts to the changing environment and can either increase or suppress the gastric inflammation. Moreover, microevolution of the virulence genes emerges in the individual patient over years. Briefly, the direct effects of H. pylori virulence factors and the chronic gastric inflammation can lead to the development of peptic ulcers or malignancy. Targeting the virulent strains in a country or region is important to explain better the clinical significance of some virulence factors and their interaction, to choose local diagnostic markers, to imply aggressive eradication strategies in the concerned patients and to provide new agents and improved regimens to control the infection.

Further reading: Helicobacter pylori

from Lyudmila Boyanova writing in Helicobacter pylori:

H. pylori resistance to antibiotics emerges most often from point mutations but also from efflux mechanisms, natural transformation, altered membrane permeability and, probably, β-lactamase. The resistance especially that to clarithromycin and quinolones often causes treatment failures. For this reason, if national or regional primary resistance rates are ≥15-20% for clarithromycin and ≥40% for metronidazole, the agents should be avoided for primary therapy of the infection unless susceptibility testing of the strains is carried out. Clarithromycin resistance-associated A2143G point mutation most often predicts eradication failures. Moreover, heteroresistance in H. pylori strains has been reported for metronidazole, clarithromycin, amoxicillin and quinolones. From <10% to >37% of the strains exhibit mixtures of genotypes. Importantly, both clarithromycin and quinolone resistance rates have grown sharply in many countries and multidrug resistance has been found in <5% in Europe and >14% in Brazil and South Korea. High primary resistance rates to clarithromycin (20->40%) and fluoroquinolones (20->33%) have been reported mostly in developed countries. Conversely, high primary resistance to metronidazole (≥76%), amoxicillin (6->30%) and tetracycline (≥15%) has been observed in some developing countries. Primary resistance and its evolution often depend on the country and national antibiotic consumption, patient characteristics such as age, sex, disease, prior antibiotic use and comorbidity, strain characteristics such as virulence as well as other factors. Post-treatment resistance rates have been usually much higher, often >3 times for clarithromycin and clarithromycin and metronidazole and ≥1.5 times for metronidazole and quinolones, compared with those of the primary resistance. In brief, a worrying evolution of antibiotic resistance in H. pylori and disturbing multidrug resistance hamper more and more the success of the eradication of the infection. Knowledge on current H. pylori resistance patterns and evolution at global and local levels is highly important to show the efficacy or need for changes in treatment regimens and to improve the overall eradication success that also means the cure of the individual patient.

Further reading: Helicobacter pylori

from Borislav Vladimirov writing in Helicobacter pylori:

Helicobacter pylori plays a main role in the development of gastritis all over the world. In addition, it is well known that H. pylori infection is associated with many nonmalignant and malignant gastrointestinal and extra-gastric diseases. H. pylori remains one of the most common causes of peptic gastro-duodenal ulcers, gastric mucosa associated lymphoid tissue (MALT) lymphoma and gastric cancer. In recent years, many clinical data have been collected about the relationship between H. pylori infection and gastro-oesophageal reflux disease (GORD), nonsteroidal anti-inflammatory drugs⁄acetylsalicylic acid-induced gastric injury and functional dyspepsia as well as about pathogenetic mechanisms of these correlations. There are also evidences confirming the role of genetic differences in host and bacterial factors and the role of environmental factors. Recent data have shown a decline in incidence and prevalence rate of peptic ulcer related to H. pylori. For patients with functional dyspepsia, eradication of H. pylori offers a modest but significant benefit. An inverse relationship between H. pylori infection and reflux oesophagitis, and Barrett oesophagus has been also confirmed. Despite of the controversial results, eradication of H. pylori infection has been recommended for nonsteroidal anti-inflammatory drugs and acetylsalicylic acid-induced gastric injury as well as for patients treated with antiplatelet therapy. The beneficial effects of H. pylori eradication on MALT lymphoma and on the prophylaxis of gastric cancer have been proven. On the other hand, an increasing amount of evidence for extra gastric manifestation of H. pylori infection has been shown.

Further reading: Helicobacter pylori