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95-426: Helicobacter pylori , previously known as Campylobacter pylori , is a gram-negative , flagellated , helical bacterium . Mutants can have a rod or curved rod shape that exhibits less virulence . Its helical body (from which the genus name Helicobacter derives) is thought to have evolved to penetrate the mucous lining of the stomach , helped by its flagella , and thereby establish infection. The bacterium

190-459: A monophyletic clade and that no loss of the outer membrane from any species from this group has occurred. The proteobacteria are a major superphylum of gram-negative bacteria, including E. coli , Salmonella , Shigella , and other Enterobacteriaceae , Pseudomonas , Moraxella , Helicobacter , Stenotrophomonas , Bdellovibrio , acetic acid bacteria , Legionella etc. Other notable groups of gram-negative bacteria include

285-427: A monophyletic taxon (though not a clade ; his definition of monophyly requires a single common ancestor but does not require holophyly , the property that all descendants be encompassed by the taxon ) and refer to the group as a subkingdom "Negibacteria". Bacteria are traditionally classified based on their Gram-staining response into the gram-positive and gram-negative bacteria. Having just one membrane,

380-652: A condition associated with a number of stomach diseases . Testing is recommended in cases of peptic ulcer disease or low-grade gastric MALT lymphoma ; after endoscopic resection of early gastric cancer ; for first-degree relatives with gastric cancer, and in certain cases of indigestion. Other indications that prompt testing for H. pylori include long term aspirin or other non-steroidal anti-inflammatory use, unexplained iron deficiency anemia , or in cases of immune thrombocytopenic purpura . Several methods of testing exist, both invasive and non-invasive. Gram-negative Within this category, notable species include

475-412: A consequence of inflammation that allows stomach acid and the digestive enzyme pepsin to overwhelm the protective mechanisms of the mucous membranes . The location of colonization of H. pylori , which affects the location of the ulcer, depends on the acidity of the stomach. In people producing large amounts of acid, H. pylori colonizes near the pyloric antrum (exit to the duodenum) to avoid

570-407: A continuation of the bacterial outer membrane which gives protection against the gastric acidity. The sheath is also the location of the origin of the outer membrane vesicles that gives protection to the bacterium from bacteriophages. Flagella motility is provided by the proton motive force provided by urease-driven hydrolysis allowing chemotactic movements towards the less acidic pH gradient in

665-657: A few conserved signature indel (CSI) in the HSP60 ( GroEL ) protein. In addition, a number of bacterial taxa (including Negativicutes , Fusobacteriota , Synergistota , and Elusimicrobiota ) that are either part of the phylum Bacillota (a monoderm group) or branches in its proximity are also found to possess a diderm cell structure. They lack the GroEL signature. The presence of this CSI in all sequenced species of conventional lipopolysaccharide-containing gram-negative bacterial phyla provides evidence that these phyla of bacteria form

760-429: A first-line immune system defence. Phagocytic leukocytes and monocytes infiltrate the site of infection, and antibodies are produced. H. pylori is able to adhere to the surface of the phagocytes and impede their action. This is responded to by the phagocyte in the generation and release of oxygen metabolites into the surrounding space. H. pylori can survive this response by the activity of catalase at its attachment to

855-463: A lifetime, or can harm the stomach and duodenal linings by inflammatory responses induced by several mechanisms associated with a number of virulence factors . Colonization can initially cause H. pylori induced gastritis , an inflammation of the stomach lining that became a listed disease in ICD11 . This will progress to chronic gastritis if left untreated. Chronic gastritis may lead to atrophy of

950-458: A major role in the pathogenesis of H. pylori . The HtrA protein enables the bacterium to transmigrate across the host cells' epithelium, and is also needed for the translocation of CagA. The virulence of H. pylori may be increased by genes of the cag pathogenicity island; about 50–70% of H. pylori strains in Western countries carry it. Western people infected with strains carrying

1045-571: A mouse model. Similarly, RecN protein plays an important role in DSB repair. An H. pylori recN mutant displays an attenuated ability to colonize mouse stomachs, highlighting the importance of recombinational DNA repair in survival of H. pylori within its host. An effective sustained colonization response is the formation of a biofilm . Having first adhered to cellular surfaces, the bacteria produce and secrete extracellular polymeric substance (EPS). EPS consists largely of biopolymers and provides

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1140-652: A multitude of species. Some of them cause primarily respiratory problems ( Klebsiella pneumoniae , Legionella pneumophila , Pseudomonas aeruginosa ), primarily urinary problems ( Escherichia coli , Proteus mirabilis , Enterobacter cloacae , Serratia marcescens ), and primarily gastrointestinal problems ( Helicobacter pylori , Salmonella enteritidis , Salmonella typhi ). Gram-negative bacteria associated with hospital-acquired infections include Acinetobacter baumannii , which cause bacteremia , secondary meningitis , and ventilator-associated pneumonia in hospital intensive-care units . Transformation

1235-435: A number of different observations, including that the gram-positive bacteria are the most sensitive to antibiotics and that the gram-negative bacteria are, in general, resistant to antibiotics, it has been proposed that the outer cell membrane in gram-negative bacteria (diderms) evolved as a protective mechanism against antibiotic selection pressure . Some bacteria such as Deinococcus , which stain gram-positive due to

1330-400: A number of gastric and non-gastric disorders. Gastric disorders due to infection begin with gastritis , or inflammation of the stomach lining. When infection is persistent, the prolonged inflammation will become chronic gastritis . Initially, this will be non-atrophic gastritis, but the damage caused to the stomach lining can bring about the development of atrophic gastritis and ulcers within

1425-408: A peculiar honeycomb appearance from being covered with funnel-like depressions or foveolae of a polygonal or hexagonal form, which vary from 0.12 to 0.25 mm. in diameter. These are the ducts of the gastric glands , and at the bottom of each may be seen one or more minute orifices, the openings of the gland tubes. Gastric glands are simple or branched tubular glands that emerge on the deeper part of

1520-503: A positive protective effect against asthma , esophageal cancer , inflammatory bowel disease (including gastroesophageal reflux disease and Crohn's disease ), and others. Some studies suggest that H. pylori plays an important role in the natural stomach ecology by influencing the type of bacteria that colonize the gastrointestinal tract. Other studies suggest that non-pathogenic strains of H. pylori may beneficially normalize stomach acid secretion, and regulate appetite. In 2023, it

1615-453: A relatively long (1186- amino acid ) protein. The cag pathogenicity island (PAI) has about 30 genes, part of which code for a complex type IV secretion system (T4SS or TFSS). The low GC-content of the cag PAI relative to the rest of the Helicobacter genome suggests the island was acquired by horizontal transfer from another bacterial species. The serine protease HtrA also plays

1710-459: A sterol glucoside that H. pylori glycosylates from the cholesterol in the gastric gland cells, and inserts it into its outer membrane. This cholesterol glucoside is important for membrane stability, morphology and immune evasion, and is rarely found in other bacteria. The enzyme responsible for this is cholesteryl α-glucosyltransferase (αCgT or Cgt), encoded by the HP0421 gene. A major effect of

1805-552: A strong host cell inflammatory response. About 4% of the genome encodes for outer membrane proteins that can be grouped into five families. The largest family includes bacterial adhesins . The other four families are porins , iron transporters, flagellum -associated proteins, and proteins of unknown function. Like other typical gram-negative bacteria, the outer membrane of H. pylori consists of phospholipids and lipopolysaccharide (LPS). The O-antigen of LPS may be fucosylated and mimic Lewis blood group antigens found on

1900-519: A toxic reaction, resulting in fever, an increased respiratory rate, and low blood pressure . That is why some infections with gram-negative bacteria can lead to life-threatening septic shock . The outer membrane protects the bacteria from several antibiotics , dyes , and detergents that would normally damage either the inner membrane or the cell wall (made of peptidoglycan ). The outer membrane provides these bacteria with resistance to lysozyme and penicillin . The periplasmic space (space between

1995-405: Is an oligomeric protein complex that causes a progressive vacuolation in the epithelial cells leading to their death. The vacuolation has also been associated with promoting intracellular reservoirs of H. pylori by disrupting the calcium channel cell membrane TRPML1 . VacA has been shown to increase the levels of COX2 , an up-regulation that increases the production of a prostaglandin indicating

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2090-689: Is an oncoprotein associated with the development of gastric cancer. H. pylori infection is associated with epigenetically reduced efficiency of the DNA repair machinery, which favors the accumulation of mutations and genomic instability as well as gastric carcinogenesis. It has been shown that expression of two DNA repair proteins, ERCC1 and PMS2 , was severely reduced once H. pylori infection had progressed to cause dyspepsia . Dyspepsia occurs in about 20% of infected individuals. Epigenetically reduced protein expression of DNA repair proteins MLH1 , MGMT and MRE11 are also evident. Reduced DNA repair in

2185-554: Is either exposed to double-strand DNA damage that must be repaired or requires some other recombination-mediated event. In particular, natural transformation is increased by DNA damage in H. pylori , and a connection exists between the DNA damage response and DNA uptake in H. pylori . This natural competence contributes to the persistence of H. pylori . H. pylori has much greater rates of recombination and mutation than other bacteria. Genetically different strains can be found in

2280-522: Is its flagellum . H. pylori has from two to seven flagella at the same polar location which gives it a high motility. The flagellar filaments are about 3 μm long, and composed of two copolymerized flagellins , FlaA and FlaB, coded by the genes flaA , and flaB . The minor flagellin FlaB is located in the proximal region and the major flagellin FlaA makes up the rest of the flagellum. The flagella are sheathed in

2375-463: Is linked to the development of 5.5% of all cases cancers worldwide. H. pylori is the only bacterium known to cause cancer. Extragastric complications that have been linked to H. pylori include anemia due either to iron deficiency or vitamin B12 deficiency , diabetes mellitus , cardiovascular illness, and certain neurological disorders. An inverse association has also been claimed with H. pylori having

2470-407: Is one of the few known types of bacterium that has a urea cycle which is uniquely configured in the bacterium. 10% of the cell is of nitrogen , a balance that needs to be maintained. Any excess is stored in urea excreted in the urea cycle. A final stage enzyme in the urea cycle is arginase , an enzyme that is crucial to the pathogenesis of H. pylori . Arginase produces ornithine and urea, which

2565-403: Is one of three processes for horizontal gene transfer , in which exogenous genetic material passes from one bacterium to another, the other two being conjugation (transfer of genetic material between two bacterial cells in direct contact) and transduction (injection of foreign DNA by a bacteriophage virus into the host bacterium). In transformation, the genetic material passes through

2660-477: Is sometimes accompanied by depression and anxiety. Where the gastritis develops into chronic gastritis, or an ulcer, the symptoms are the same and can include indigestion , stomach or abdominal pains, nausea, bloating , belching , feeling hunger in the morning, feeling full too soon, and sometimes vomiting , heartburn, bad breath, and weight loss. Complications of an ulcer can cause severe signs and symptoms such as black or tarry stool indicative of bleeding into

2755-416: Is supported by transformation -mediated recombinational repair , that contributes to successful colonization. H. pylori is naturally competent for transformation. While many organisms are competent only under certain environmental conditions, such as starvation, H. pylori is competent throughout logarithmic growth. Transformation (the transfer of DNA from one bacterial cell to another through

2850-588: Is the most abundant protein, its expression representing about 10% of the total protein weight. H. pylori possesses five major outer membrane protein families. The largest family includes known and putative adhesins . The other four families are porins , iron transporters, flagellum -associated proteins, and proteins of unknown function. Like other typical gram-negative bacteria, the outer membrane of H. pylori consists of phospholipids and lipopolysaccharide (LPS). The O-antigen of LPS may be fucosylated and mimic Lewis blood group antigens found on

2945-415: Is the third highest cause of worldwide cancer mortality as of 2018. Because of the usual lack of symptoms, when gastric cancer is finally diagnosed it is often fairly advanced. More than half of gastric cancer patients have lymph node metastasis when they are initially diagnosed. Chronic inflammation that is a feature of cancer development is characterized by infiltration of neutrophils and macrophages to

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3040-540: The CDC ), if any, governs the document being written. This is further explained at Gram staining § Orthographic note . Gastric mucosa The gastric mucosa is the mucous membrane layer of the stomach , which contains the gastric pits , to which the gastric glands empty. In humans, it is about one mm thick, and its surface is smooth, soft, and velvety. It consists of simple secretory columnar epithelium , an underlying supportive layer of loose connective tissue called

3135-1020: The antimicrobial enzyme lysozyme produced by animals as part of their innate immune system . Furthermore, the outer leaflet of this membrane contains a complex lipopolysaccharide (LPS) whose lipid A component can trigger a toxic reaction when the bacteria are lysed by immune cells. This reaction may lead to septic shock , resulting in low blood pressure , respiratory failure , reduced oxygen delivery , and lactic acidosis . Several classes of antibiotics have been developed to target gram-negative bacteria, including aminopenicillins , ureidopenicillins , cephalosporins , beta-lactam - betalactamase inhibitor combinations (such as piperacillin-tazobactam ), folate antagonists , quinolones , and carbapenems . Many of these antibiotics also cover gram-positive bacteria. The antibiotics that specifically target gram-negative organisms include aminoglycosides , monobactams (such as aztreonam ), and ciprofloxacin . Conventional gram-negative (LPS-diderm) bacteria display

3230-602: The atmosphere . It contains a hydrogenase that can produce energy by oxidizing molecular hydrogen (H 2 ) made by intestinal bacteria . H. pylori can be demonstrated in tissue by Gram stain , Giemsa stain , H&E stain , Warthin-Starry silver stain , acridine orange stain , and phase-contrast microscopy . It is capable of forming biofilms . Biofilms help to hinder the action of antibiotics and can contribute to treatment failure. To successfully colonize its host, H. pylori uses many different virulence factors including oxidase , catalase , and urease . Urease

3325-410: The cag PAI have a stronger inflammatory response in the stomach and are at a greater risk of developing peptic ulcers or stomach cancer than those infected with strains lacking the island. Following attachment of H. pylori to stomach epithelial cells, the type IV secretion system expressed by the cag PAI "injects" the inflammation -inducing agent, peptidoglycan, from their own cell walls into

3420-416: The cag pathogenicity island remains intact in the coccoid form. Some of these antibiotic resistant cells may remain in the host as persister cells . Following eradication, the persister cells can cause a recurrence of the infection. Bacteria can detach from the biofilm to relocate and colonize elsewhere in the stomach to form other biofilms. Colonization with H. pylori is not a disease in itself, but

3515-474: The cyanobacteria , spirochaetes , green sulfur , and green non-sulfur bacteria . Medically-relevant gram-negative diplococci include the four types that cause a sexually transmitted disease ( Neisseria gonorrhoeae ), a meningitis ( Neisseria meningitidis ), and respiratory symptoms ( Moraxella catarrhalis , A coccobacillus Haemophilus influenzae is another medically relevant coccal type. Medically relevant gram-negative bacilli include

3610-476: The gastric pits, inside the gastric areas and outlined by the folds of the mucosa. The gastric glands in the cardiac region of the stomach are known as cardiac glands. In the pyloric region the glands are known as pyloric glands, and in the rest of the stomach they are called gastric glands. Several types of endocrine cells are found in the gastric glands. The pyloric glands contain gastrin -producing cells ( G cells ); this hormone stimulates acid production from

3705-403: The lamina propria , and the muscularis mucosae , a thin layer of muscle that separates the mucosa from the underlying submucosa. In its fresh state, it is of a pinkish tinge at the pyloric end and of a red or reddish-brown color over the rest of its surface. In infancy it is of a brighter hue, the vascular redness being more marked. It is thin at the cardiac extremity, but thicker toward

3800-416: The model organism Escherichia coli , along with various pathogenic bacteria , such as Pseudomonas aeruginosa , Chlamydia trachomatis , and Yersinia pestis . They pose significant challenges in the medical field due to their outer membrane, which acts as a protective barrier against numerous antibiotics (including penicillin ), detergents that would normally damage the inner cell membrane, and

3895-424: The urea present in the stomach to produce ammonia and bicarbonate , which are released into the bacterial cytosol and the surrounding environment, creating a neutral area. The decreased acidity (higher pH) changes the mucus layer from a gel-like state to a more viscous state that makes it easier for the flagella to move the bacteria through the mucosa and attach to the gastric epithelial cells. Helicobacter pylori

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3990-446: The 30 strains, and represent the universal core . The remaining 991 OGs correspond to the accessory genome in which 277 OGs are unique to one strain. There are eleven restriction modification systems in the genome of H. pylori . This is an unusually high number providing a defence against bacteriophages . Single-cell transcriptomics using single-cell RNA-Seq gave the complete transcriptome of H. pylori which

4085-426: The acid-secreting parietal cells at the fundus (near the entrance to the stomach). G cells express relatively high levels of PD-L1 that protects these cells from H. pylori -induced immune destruction. In people producing normal or reduced amounts of acid, H. pylori can also colonize the rest of the stomach. The inflammatory response caused by bacteria colonizing near the pyloric antrum induces G cells in

4180-577: The antrum to secrete the hormone gastrin , which travels through the bloodstream to parietal cells in the fundus. Gastrin stimulates the parietal cells to secrete more acid into the stomach lumen, and over time increases the number of parietal cells, as well. The increased acid load damages the duodenum, which may eventually lead to the formation of ulcers. Helicobacter pylori is a class I carcinogen , and potential cancers include gastric mucosa-associated lymphoid tissue (MALT) lymphomas and gastric cancer . Less commonly, diffuse large B-cell lymphoma of

4275-471: The bacteria enables the formation of a biofilm which furthers persistent colonisation. In the layers of the biofilm, H. pylori can escape from the actions of antibiotics, and also be protected from host-immune responses. In the biofilm, H. pylori can change the flagella to become adhesive structures. In addition to using chemotaxis to avoid areas of high acidity (low pH), H. pylori also produces large amounts of urease , an enzyme which breaks down

4370-414: The bacteria to become locally established. Arginase promotes the persistence of infection by consuming arginine; arginine is used by macrophages to produce nitric oxide, which has a strong antimicrobial effect. The ammonia produced to regulate pH is toxic to epithelial cells. H. pylori must make attachment with the epithelial cells to prevent its being swept away with the constant movement and renewal of

4465-491: The cause of rectal bleeding, anemia, constipation, diarrhea, weight loss, and abdominal pain. Virulence factors help a pathogen to evade the immune response of the host, and to successfully colonize . The many virulence factors of H. pylori include its flagella, the production of urease, adhesins, serine protease HtrA (high temperature requirement A), and the major exotoxins CagA and VacA . The presence of VacA and CagA are associated with more advanced outcomes . CagA

4560-486: The cell, the CagA protein is phosphorylated on tyrosine residues by a host cell membrane-associated tyrosine kinase (TK). CagA then allosterically activates protein tyrosine phosphatase / protooncogene Shp2 . These proteins are directly toxic to cells lining the stomach and signal strongly to the immune system that an invasion is under way. As a result of the bacterial presence, neutrophils and macrophages set up residence in

4655-400: The cells in the biofilm matrix allowing the transport of nutrients, enzymes, metabolites, and waste. Cells in the deep layers may be nutritionally deprived and enter into the coccoid dormant-like state. By changing the shape of the bacterium to a coccoid form, the exposure of LPS (targeted by antibiotics) becomes limited, and so evades detection by the immune system. It has also been shown that

4750-605: The consensus Shine–Dalgarno sequence in H. pylori . The proteome of H. pylori has been systematically analyzed and more than 70% of its proteins have been detected by mass spectrometry , and other methods. About 50% of the proteome has been quantified, informing of the number of protein copies in a typical cell. Studies of the interactome have identified more than 3000 protein-protein interactions . This has provided information of how proteins interact with each other, either in stable protein complexes or in more dynamic, transient interactions, which can help to identify

4845-628: The depletion of host cholesterol by Cgt is to disrupt cholesterol-rich lipid rafts in the epithelial cells. Lipid rafts are involved in cell signalling and their disruption causes a reduction in the immune inflammatory response, particularly by reducing interferon gamma . Cgt is also secreted by the type IV secretion system, and is secreted in a selective way so that gastric niches where the pathogen can thrive are created. Its lack has been shown to give vulnerability from environmental stress to bacteria, and also to disrupt CagA-mediated interactions. Colonization induces an intense anti-inflammatory response as

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4940-724: The development of different mechanisms of tolerance that enable the persistence of H. pylori . These mechanisms can also help to overcome the effects of antibiotics. H. pylori has to not only survive the harsh gastric acidity but also the sweeping of mucus by continuous peristalsis , and phagocytic attack accompanied by the release of reactive oxygen species . All organisms encode genetic programs for response to stressful conditions including those that cause DNA damage. Stress conditions activate bacterial response mechanisms that are regulated by proteins expressed by regulator genes . The oxidative stress can induce potentially lethal mutagenic DNA adducts in its genome. Surviving this DNA damage

5035-420: The diderm bacteria in which the outer cell membrane is made up of mycolic acid (e. g. Mycobacterium ). The conventional LPS- diderm group of gram-negative bacteria (e.g., Pseudomonadota , Aquificota , Chlamydiota , Bacteroidota , Chlorobiota , " Cyanobacteria ", Fibrobacterota , Verrucomicrobiota , Planctomycetota , Spirochaetota , Acidobacteriota ; " Hydrobacteria ") are uniquely identified by

5130-527: The enhanced production of free radicals near H. pylori and an increased rate of host cell mutation . The other proposed mechanism has been called a "perigenetic pathway", and involves enhancement of the transformed host cell phenotype by means of alterations in cell proteins, such as adhesion proteins. H. pylori has been proposed to induce inflammation and locally high levels of tumor necrosis factor (TNF), also known as tumor necrosis factor alpha (TNFα)), and/or interleukin 6 (IL-6). According to

5225-402: The enzyme urease breaks down into carbonic acid and ammonia. Urease is the bacterium’s most abundant protein, accounting for 10–15% of the bacterium's total protein content. Its expression is not only required for establishing initial colonization in the breakdown of urea to carbonic acid and ammonia, but is also essential for maintaining chronic infection. Ammonia reduces stomach acidity, allowing

5320-482: The epithelial cells. The injected peptidoglycan is recognized by the cytoplasmic pattern recognition receptor (immune sensor) Nod1, which then stimulates expression of cytokines that promote inflammation. The type-IV secretion apparatus also injects the cag PAI-encoded protein CagA into the stomach's epithelial cells, where it disrupts the cytoskeleton , adherence to adjacent cells, intracellular signaling, cell polarity , and other cellular activities. Once inside

5415-434: The expression of vimentin . Vimentin is important in the epithelial–mesenchymal transition associated with the progression of tumors. CagA (cytotoxin-associated antigen A) is a major virulence factor for H. pylori , an oncoprotein that is encoded by the cagA gene. Bacterial strains with the cagA gene are associated with the ability to cause ulcers, MALT lymphomas, and gastric cancer. The cagA gene codes for

5510-518: The following characteristics : Along with cell shape, Gram staining is a rapid diagnostic tool and once was used to group species at the subdivision of Bacteria. Historically , the kingdom Monera was divided into four divisions based on Gram staining: Firmacutes (+), Gracillicutes (−), Mollicutes (0) and Mendocutes (var.). Since 1987, the monophyly of the gram-negative bacteria has been disproven with molecular studies . However some authors, such as Cavalier-Smith still treat them as

5605-424: The framework for the biofilm structure. H. pylori helps the biofilm formation by altering its flagella into adhesive structures that provide adhesion between the cells. Layers of aggregated bacteria as microcolonies accumulate to thicken the biofilm. The matrix of EPS prevents the entry of antibiotics and immune cells, and provides protection from heat and competition from other microorganisms. Channels form between

5700-471: The functions of the protein. This in turn helps researchers to find out what the function of uncharacterized proteins is, e.g. when an uncharacterized protein interacts with several proteins of the ribosome (that is, it is likely also involved in ribosome function). About a third of all ~1,500 proteins in H. pylori remain uncharacterized and their function is largely unknown. An infection with Helicobacter pylori can either have no symptoms even when lasting

5795-445: The gastric epithelium, which favors the accumulation of pro-inflammatory cytokines , reactive oxygen species (ROS) and reactive nitrogen species (RNS) that cause DNA damage . The oxidative DNA damage and levels of oxidative stress can be indicated by a biomarker, 8-oxo-dG . Other damage to DNA includes double-strand breaks . Small gastric and colorectal polyps are adenomas that are more commonly found in association with

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5890-492: The gastric epithelium. H. pylori forms blebs from the outer membrane that pinch off as outer membrane vesicles to provide an alternative delivery system for virulence factors including CagA. A Helicobacter cysteine-rich protein HcpA is known to trigger an immune response, causing inflammation. A Helicobacter pylori virulence factor DupA is associated with the development of duodenal ulcers. The need for survival has led to

5985-444: The gastric epithelium. Helicobacter pylori consists of a large diversity of strains, and hundreds of genomes have been completely sequenced . The genome of the strain 26695 consists of about 1.7 million base pairs , with some 1,576 genes. The pan-genome , that is the combined set of 30 sequenced strains, encodes 2,239 protein families ( orthologous groups OGs). Among them, 1,248 OGs are conserved in all

6080-408: The gland ducts is of the same character and is continuous with the general epithelial lining of the stomach. The sodium-iodide symporter (SIP) is expressed in all the surface mucous cells (at the basolateral membrane) but not in the mucous neck cells. SIP mediates the transport of iodide from the bloodstream and secretes it into the gastric lumen where it is taken up in the gastric juice. Its role

6175-487: The gram-positive bacteria are also known as monoderm bacteria , while gram-negative bacteria, having two membranes, are also known as diderm bacteria . It was traditionally thought that the groups represent lineages, i.e., the extra membrane only evolved once, such that gram-negative bacteria are more closely related to one another than to any gram-positive bacteria. While this is often true, the classification system breaks down in some cases, with lineage groupings not matching

6270-444: The intervening medium) appears to be part of an adaptation for DNA repair . Homologous recombination is required for repairing double-strand breaks (DSBs). The AddAB helicase-nuclease complex resects DSBs and loads RecA onto single-strand DNA (ssDNA), which then mediates strand exchange, leading to homologous recombination and repair. The requirement of RecA plus AddAB for efficient gastric colonization suggests that H. pylori

6365-830: The intervening medium, and uptake is completely dependent on the recipient bacterium. As of 2014 about 80 species of bacteria were known to be capable of transformation, about evenly divided between gram-positive and gram-negative bacteria; the number might be an overestimate since several of the reports are supported by single papers. Transformation has been studied in medically important gram-negative bacteria species such as Helicobacter pylori , Legionella pneumophila , Neisseria meningitidis , Neisseria gonorrhoeae , Haemophilus influenzae and Vibrio cholerae . It has also been studied in gram-negative species found in soil such as Pseudomonas stutzeri , Acinetobacter baylyi , and gram-negative plant pathogens such as Ralstonia solanacearum and Xylella fastidiosa . One of

6460-472: The less acidic mucosa by use of their flagella . Three strains studied showed a variation in length from 2.8–3.3 μm but a fairly constant diameter of 0.55–0.58 μm. H. pylori can convert from a helical to an inactive coccoid form that can evade the immune system, and that may possibly become viable, known as viable but nonculturable (VBNC). Helicobacter pylori is microaerophilic – that is, it requires oxygen , but at lower concentration than in

6555-453: The mucosa. The mucus layer is about 300 μm thick, and the helical shape of H. pylori aided by its flagella helps it to burrow through this layer where it colonises a narrow region of about 25 μm closest to the epithelial cell layer, where the pH is near to neutral. They further colonise the gastric pits and live in the gastric glands . Occasionally the bacteria are found inside the epithelial cells themselves. The use of quorum sensing by

6650-569: The mucosal damage induced by H. pylori gastritis. Larger polyps can in time become cancerous. A modest association of H. pylori has been made with the development of colorectal cancers , but as of 2020 causality had yet to be proved. Most people infected with H. pylori never experience any symptoms or complications, but will have a 10% to 20% risk of developing peptic ulcers or a 0.5% to 2% risk of stomach cancer. H. pylori induced gastritis may present as acute gastritis with stomach ache , nausea , and ongoing dyspepsia (indigestion) that

6745-473: The mucus. To give them this adhesion, bacterial outer membrane proteins as virulence factors called adhesins are produced. BabA (blood group antigen binding adhesin) is most important during initial colonization, and SabA (sialic acid binding adhesin) is important in persistence. BabA attaches to glycans and mucins in the epithelium. BabA (coded for by the babA2 gene) also binds to the Lewis b antigen displayed on

6840-435: The parietal cells. Enterochromaffin-like cells (ECLs), found in the oxyntic glands release histamine , which also is a powerful stimulant of the acid secretion. The surface of the mucous membrane is covered by a single layer of columnar epithelium . This epithelium commences very abruptly at the cardiac orifice , where there is a sudden transition from the stratified epithelium of the esophagus . The epithelial lining of

6935-509: The peri-plasmic space. Other classes of drugs that have gram negative spectrum include cephalosporins , monobactams ( aztreonam ), aminoglycosides, quinolones , macrolides , chloramphenicol , folate antagonists , and carbapenems . The adjectives gram-positive and gram-negative derive from the surname of Hans Christian Gram , a Danish bacteriologist; as eponymous adjectives , their initial letter can be either capital G or lower-case g , depending on which style guide (e.g., that of

7030-501: The phagocytic cell surface. Catalase decomposes hydrogen peroxide into water and oxygen, protecting the bacteria from toxicity. Catalase has been shown to almost completely inhibit the phagocytic oxidative response. It is coded for by the gene katA . TNF-inducing protein alpha (Tipα) is a carcinogenic protein encoded by HP0596 unique to H. pylori that induces the expression of tumor necrosis factor . Tipα enters gastric cancer cells where it binds to cell surface nucleolin , and induces

7125-419: The presence of a thick peptidoglycan layer, but also possess an outer cell membrane are suggested as intermediates in the transition between monoderm (gram-positive) and diderm (gram-negative) bacteria. The diderm bacteria can also be further differentiated between simple diderms lacking lipopolysaccharide (LPS); the archetypical diderm bacteria, in which the outer cell membrane contains lipopolysaccharide; and

7220-434: The presence of increased DNA damage increases carcinogenic mutations and is likely a significant cause of gastric carcinogenesis. These epigenetic alterations are due to H. pylori -induced methylation of CpG sites in promoters of genes and H. pylori -induced altered expression of multiple microRNAs . Two related mechanisms by which H. pylori could promote cancer have been proposed. One mechanism involves

7315-526: The primary TSSs are also antisense TSSs, indicating that – similar to E. coli – antisense transcription occurs across the entire H. pylori genome. At least one antisense TSS is associated with about 46% of all open reading frames , including many housekeeping genes . About 50% of the 5 ′ UTRs (leader sequences) are 20–40 nucleotides (nt) in length and support the AAGGag motif located about 6 nt (median distance) upstream of start codons as

7410-408: The proposed perigenetic mechanism, inflammation-associated signaling molecules, such as TNF, can alter gastric epithelial cell adhesion and lead to the dispersion and migration of mutated epithelial cells without the need for additional mutations in tumor suppressor genes , such as genes that code for cell adhesion proteins. The first virulence factor of Helicobacter pylori that enables colonization

7505-401: The pylorus. During the contracted state of the organ it is thrown into numerous folds or rugae , which, for the most part, have a longitudinal direction, and are most marked toward the pyloric end of the stomach, and along the greater curvature . These folds are entirely obliterated when the organ becomes distended . When examined with a lens, the inner surface of the mucous membrane presents

7600-577: The same host, and also in different regions of the stomach. An overall response to multiple stressors can result from an interaction of the mechanisms. RuvABC proteins are essential to the process of recombinational repair, since they resolve intermediates in this process termed Holliday junctions . H. pylori mutants that are defective in RuvC have increased sensitivity to DNA-damaging agents and to oxidative stress, exhibit reduced survival within macrophages, and are unable to establish successful infection in

7695-459: The several unique characteristics of gram-negative bacteria is the structure of the bacterial outer membrane . The outer leaflet of this membrane contains lipopolysaccharide (LPS), whose lipid A portion acts as an endotoxin . If gram-negative bacteria enter the circulatory system , LPS can trigger an innate immune response , activating the immune system and producing cytokines (hormonal regulators). This leads to inflammation and can cause

7790-426: The staining result. Thus, Gram staining cannot be reliably used to assess familial relationships of bacteria. Nevertheless, staining often gives reliable information about the composition of the cell membrane, distinguishing between the presence or absence of an outer lipid membrane . Of these two structurally distinct groups of prokaryotic organisms, monoderm prokaryotes are thought to be ancestral. Based upon

7885-475: The stomach is a risk. Infection with H. pylori is responsible for around 89 per cent of all gastric cancers, and is linked to the development of 5.5 per cent of all cases of cancer worldwide. Although the data varies between different countries, overall about 1% to 3% of people infected with Helicobacter pylori develop gastric cancer in their lifetime compared to 0.13% of individuals who have had no H. pylori infection. H. pylori -induced gastric cancer

7980-456: The stomach itself or the duodenum (the nearest part of the intestine). At this stage, the risk of developing gastric cancer is high. However, the development of a duodenal ulcer confers a comparatively lower risk of cancer. Helicobacter pylori is a class 1 carcinogenic bacteria , and potential cancers include gastric MALT lymphoma and gastric cancer . Infection with H. pylori is responsible for an estimated 89% of all gastric cancers and

8075-415: The stomach lining, and the development of peptic ulcers (gastric or duodenal). These changes may be seen as stages in the development of gastric cancer , known as Correa's cascade . Extragastric complications that have been linked to H. pylori include anemia due either to iron-deficiency or vitamin B12 deficiency, diabetes mellitus, cardiovascular, and certain neurological disorders. Peptic ulcers are

8170-424: The stomach or duodenum; blood - either red or coffee-ground colored in vomit; persistent sharp or severe abdominal pain; dizziness, and a fast heartbeat. Bleeding is the most common complication. In cases caused by H. pylori there was a greater need for hemostasis often requiring gastric resection. Prolonged bleeding may cause anemia leading to weakness and fatigue. Inflammation of the pyloric antrum, which connects

8265-494: The stomach to the duodenum, is more likely to lead to duodenal ulcers, while inflammation of the corpus may lead to a gastric ulcer. Stomach cancer can cause nausea, vomiting, diarrhoea, constipation, and unexplained weight loss. Gastric polyps are adenomas that are usually asymptomatic and benign, but may be the cause of dyspepsia, heartburn, bleeding from the stomach, and, rarely, gastric outlet obstruction. Larger polyps may have become cancerous . Colorectal polyps may be

8360-438: The strain that infects a person can predict the outcome. VacA (vacuolating cytotoxin autotransporter) is another major virulence factor encoded by the vacA gene. All strains of H. pylori carry this gene but there is much diversity, and only 50% produce the encoded cytotoxin. The four main subtypes of vacA are s1/m1, s1/m2, s2/m1, and s2/m2 . s1/m1 and s1/m2 are known to cause an increased risk of gastric cancer. VacA

8455-484: The surface of the epithelial cells. Adherence via BabA is acid sensitive and can be fully reversed by a decreased pH. It has been proposed that BabA's acid responsiveness enables adherence while also allowing an effective escape from an unfavorable environment such as a low pH that is harmful to the organism. SabA (coded for by the sabA gene) binds to increased levels of sialyl-Lewis antigen expressed on gastric mucosa. The outer membrane contains cholesterol glucoside ,

8550-686: The tissue to fight the bacteria assault. Pathogenic strains of H. pylori have been shown to activate the epidermal growth factor receptor (EGFR), a membrane protein with a TK domain . Activation of the EGFR by H. pylori is associated with altered signal transduction and gene expression in host epithelial cells that may contribute to pathogenesis. A C-terminal region of the CagA protein (amino acids 873–1002) has also been suggested to be able to regulate host cell gene transcription , independent of protein tyrosine phosphorylation. A great deal of diversity exists between strains of H. pylori , and

8645-403: The two cell membranes) also contains enzymes which break down or modify antibiotics. Drugs commonly used to treat gram negative infections include amino, carboxy and ureido penicillins ( ampicillin , amoxicillin , pipercillin , ticarcillin ). These drugs may be combined with beta-lactamase inhibitors to combat the presence of enzymes that can digest these drugs (known as beta-lactamases ) in

8740-425: The world's population is infected with H. pylori but only a few strains are pathogenic . H pylori is a helical bacterium having a predominantly helical shape , also often described as having a spiral or S shape. Its helical shape is better suited for progressing through the viscous mucosa lining of the stomach , and is maintained by a number of enzymes in the cell wall's peptidoglycan . The bacteria reach

8835-464: Was estimated that about two-thirds of the world's population was infected with H. pylori , being more common in developing countries . The prevalence has declined in many countries due to eradication treatments with antibiotics and proton-pump inhibitors , and with increased standards of living . Helicobacter pylori is a species of gram-negative bacteria in the Helicobacter genus. About half

8930-620: Was first identified as the causal agent of gastric ulcers in 1983 by Australian physician-scientists Barry Marshall and Robin Warren . In 2005, they were awarded the Nobel Prize in Physiology or Medicine for their discovery. Infection of the stomach with H. pylori is not the cause of illness itself: over half of the global population is infected, but most individuals are asymptomatic. Persistent colonization with more virulent strains can induce

9025-500: Was published in 2010. This analysis of its transcription confirmed the known acid induction of major virulence loci, including the urease (ure) operon and the Cag pathogenicity island (PAI). A total of 1,907  transcription start sites 337 primary operons , and 126 additional suboperons, and 66 mono cistrons were identified. Until 2010, only about 55 transcription start sites (TSSs) were known in this species. 27% of

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