Done by: Tala Alsaket Ruba Al-mgableh Salam Hiasat Lujain Arabiat Helicobacter pylori Done by: Tala Alsaket Ruba Al-mgableh Salam Hiasat Lujain Arabiat

Introduction Helicobacter pylori is a Gram-negative member of the Epsilon-proteo-bacteria class. Over 50% of the global human population is colonized with H.pylori . Infection is more prevalent in developing countries. To colonize the stomach successfully, H. pylori must survive the acidic pH in the lumen of the stomach , move through the mucus lining of the gastric tissue via chemotactic flagellar-mediated motility.

Attach to gastric epithelial cells using a repertoire of adhesins, and deploy cytotoxins to alter the gastric environment. Although the first isolation of the microorganism was in 1983 by Marshall and Warren.

Virulence factors

Urease Urease activity and association with gastric mucosal cells are important virulence factors of H. pylori. Urease activity is perhaps the best characterized of these factors. Urease activity creates a cloud of ammonia around the bacterium, thus neutralizing the lethal effects of gastric acid. The process, which we term "altruistic autolysis," involves release of urease by genetically programmed autolysis with adsorption of the released urease onto the surface of neighboring intact bacteria.

Cag-PAI The presence of cagA gene has been associated with higher grades of inflammation, which may lead to the development of the most severe gastrointestinal diseases, such as peptic ulcer disease. CagPAI is a 40 kb region of chromosomal DNA encoding approximately 31 genes that forms a type IV secretion system and can be divided into two regions, cag I and cag II. This secretion system forms a pilus that delivers CagA.

The EPIYA-C segment variably multiplies (mostly one to three times) in tandem among different Western CagA species. There is an important relationship between strains vacA s1m1 and CagA positive has also been reported. Although located in different genomic regions, the cagA gene is strongly associated with the cytotoxic activity of VacAand strains expressing the combination of these alleles and cagA are considered the most virulent causing more severe epithelial damage, which can be associated with the development of the most severe gastric diseases.

Vacuolating Cytotoxin Gene (vacA) VacA is a cytotoxin secreted from bacteria as a large 140-kDa polypeptide and latter trimmed at both ends to finally deliver it in an active form to host cells, where it exerts its activity. The gene encoding VacA is present in all H. pylori strains and displays allelic diversity in three main regions, the s (signal), the i (intermediate), and the m (middle) regions, and consequently, the cytotoxic activity of the toxin varies between strains. . Different combinations of two major alleles of each region (s1, s2, i1, i2, m1, m2) may exist, which results in VacA toxins with distinct capability of inducing vacuolation in epithelial cells. While vacA s1/m1 strains are consistently vacuolating and vacA s2/m2 strains are non-vacuolating.

VacA is also capable of inducing membrane-channel formation, cytochrome C release from mitochondria and binding to cell membrane receptors activating a proinflammatory response.

Blood group antigen-binding adhesion (BabA) BabA is the best-characterized adhesion . Some researchers have demonstrated that there is an association between babA2-positive genotypes and occurrence of peptic ulcer disease, although it remains controversial. The study performed by Zambon showed that babA2 and cagA, and vacA s1 and m1 coexpressed by the same H. pylori strain work synergistically in worsening inflammation and may be a potential risk of intestinal metaplasia. A recent study with Iranian patients reported that babA2 prevalence was significantly higher in GC patients (95%) when compared with DU patients (18.1%) and non-ulcer dyspepsia subjects (26.1%).

Causes The infections are thought to spread from one person’s mouth to another. They may also be transferred from feces to the mouth, when a person does not wash their hands thoroughly after using the bathroom H. pylori can also spread through contact with contaminated water or food. they penetrate the stomach’s mucous lining and generate substances that neutralize stomach acids. This makes the stomach cells more vulnerable to the harsh acids.

Symptoms Typical symptoms of H.pylori infection include gnawing or burning sensation. Many infected individuals may have no symptoms. other infected people may experience some: belching, bloating, nausea and vomiting as well as abdominal discomfort. Sometimes serious infection may cause nausea and vomiting including vomiting blood. Also chronic infection may suppress natural body defenses.

People at risk of H.pylori infection Children are more likely to develop an H. pylori infection. Their risk is higher mostly due to lack of proper hygiene. Your risk is higher if you: - live in a developing country - share housing with others who are infected with H. pylori - live in overcrowded housing - have no access to hot water, which can help to keep areas clean and free from bacteria

Diagnosis of H.pylori There are many tests to detect H.pylori infection include: -histology -rapid Urease test -blood anti-body test

Benefits of treatment H.pylori eradication in patients yield a superior healing rates in duodenal ulcers. H.pylori treatment decreases recurrent bleeding by (17%). H.pylori treatment achieves tumor regression in 60-90% of patients with gastric MALT lymphoma. H.pylori eradication could be associated with worsening, no change nor improvement of GERD.

NON-pharmacological treatment Cranberry juice consider successful in preventing the adhesion of bacteria to the lining of the GI or any site of infection. consumption of garlic for long periods of time did not affect the occurrence of H. pylori infection. eradication rate was significantly higher in these patients than those who ingested curcumin

pharmacologic treatment Primary treatment of h.pylori include: PPI, calrithromycin and amoxicillin or metronidazole (calrithromycin, based-triple therapy) for 14 days. PPI, H2-recepter blocker, bismuth, metronidazole and tetracycline for 10-14 days. Sequential therapy include: PPI and amoxicillin for 5 days followed by PPI, clarithromycin and trinidazole for other 5 days.

Resistance Antibiotic resistance is regionally variable, Also H.pylori eradication rates declining globally. The main mechanisms leading to amoxicillin resistance of H. pylori are alterations in penicillin-binding proteins, decreased membrane permeability of antibiotics into the bacterial cell. Clarithromycin resistance generally caused by point mutations in the 23S rRNA gene, the most frequent is A2143G followed by A2142G and A2142CThese mutations prevent the macrolide from binding. Metronidazole resistance due to null mutations in the rdxA gene, this gene codes for an oxygen-insensitive.

Resistance Resistance to rifabutin is generally caused by point mutation in codons 524–545 or codon 585 of the rpoB gene, cross resistance between rifabutin and rifampin has been reported. Tetracycline resistance occurs because of enhancing efflux mechanisms which leads to decrease the concentrations of tetracycline inside the bacterial cells. Also, protection proteins increase tetracycline resistance either by decreasing the affinity of ribosomes for tetracycline or by releasing the bound antibiotic from the ribosome. Levofloxacin resistance by point mutations of gyrA, which codes for DNA gyrase, have been identified in the quinolone-resistant determination region with the major mutations being found at position in the codons coding for amino acid 87, 88, 91 or 97.

Summary This infection occurs worldwide, but there are a certain countries or regions with higher prevalence of h.pylori infection. Many studies shown that a poor socioeconomic state contribute in increasing the risk of h.pylori infection. Helicobacter pylori consider one of the most important factors causes peptic ulcers, chronic gastritis and gastric neoplasms. The international agency of cancer first classified it as a group1 carcinogen.