Stomach

Human

Microbes

• Rhinovirus
• Tropheryma whipplei
• Clostridium difficile
• Lactobacillus johnsonii
• Vibrio vulnificus
• Borrelia afzelii
• Bacillus cereus
• Helicobacter pylori

Helicobacter pylori

Classification

Domain             Phylum	        Class	                        Order	              Family	           Genus	Species

Bacteria Proteobacteria Epsilon Proteobacteria Campylobacterales Helicobacteraceae Helicobacter pylori

Significant History of H. pylori

The discovery of Helicobacter pylori as an infectious agent responsible for peptic ulcer disease marked a turning point in our understanding of gastrointestinal microbial ecology and disease. The accepted medical paradigm about stomach ulcers believed that no bacterium can live in human stomach and stomach ulcers occurred when excess acid damaged the gastric mucosa, and treatment should be aimed at reducing or neutralizing that acid. However, in 1982, Barry Marshall and J. Robin Warren isolated a new bacterium and showed that it caused gastritis and stomach ulcers, diseases that affect millions of humans worldwide (4). They cultured a new slow-growing Campylobacter-like organism since it resembled Campylobacter in several respects, including curved rod-shaped morphology, growth on rich media under microaerophilic conditions, failure to ferment glucose, sensitivity to metronidazole, and G+C content of 34%. The Campylobacter-like organism was first referred to as “pyloric Campylobacter” and in 1985, it was validated as Campylobacter pyloridis. In 1987, the specific epithet was revised to Campylobacter pylori to conform to the correct Latin genitive of the noun pylorus. Even though C. pylori resembles Campylobacter in many aspects, it differs in important features such as flagellum morphology, fatty acid content, and 16S rRNA sequence. C. pylori was transferred to a new genus, Helicobacter, and renamed Helicobacter pylori in 1989. Helicobacter pylori was the first member of the new genus and the genus Helicobacter was expanded tremendously and new species are regularly included. The majority of these new Helicobacter species are found in the stomachs and intestines of different animals. (2, 3) Although isolating H. pylori was significant enough, they still did not prove whether the bacteria were the cause of the inflammation with which they were associated or whether they occurred as a result of it. Using Koch’s postulates, Marshall and another volunteer confirmed the connection between H. pylori and gastritis, but since neither scientist developed an ulcer, that link was still unproven. Eventually, the connection between H. pylori and ulcers was deduced from epidemiological studies showed an increased incidence of ulcers in persons infected with the bacteria (4).

Description and structure

H. pylori is an S-shaped bacterium with 1 to 3 turns, 0.5 X 5 μm in length, with a tuft of 5 to 7 polar sheathed flagella. The cell is a gram-negative bacterium that consists of outer and inner, or plasma, membranes separated by the periplasm of approximately 30nm thickness (1). Its morphology is similar to C. jejuni; it was initially named “pyloric Campylobacter” for this reason (6). The dense cytoplasm contains nucleoid material and ribosomes. Also, there is an electron-lucent area is located in the terminal regions and these regions. Associated with this region and located near the flagella insertion site is a “polar membrane.” This is an additional electron-dense band 6 to 8 nm thick located 20nm below the plasmic membrane yet linked to it. ATPase molecules are probably located at this site to generate energy for motility or cell wall synthesis (1).

Growth Conditions

H. pylori is usually located within the thick mucous layer in close proximity to gastric epithelial cells, which is an acid environment where the most of the bacteria can’t survive (1). Also, it typically grow under microaerobic conditions at 37°C which is about body temperature. No growth is observed in aerobic conditions (3). A weakening of the mucous barrier by H. pylori, leading in some cases to its collapse, has been proposed as H. pylori possesses a gene that is almost identical to a mucinase gene of Vibrio cholerae. Such mucinase activity may be responsible for the dissolution of the net-like structure of the mucus and the variously sized cave-like structure of the mucus and the variously sized cave-like clear areas surrounding H. pylori as observed in vivo with electron microscopic techniques. However, studies in vitro suggest that the loss of gel structure might also arise from high local pH generated by the urease activity of H. pylori rather than by mucolytic activity. Furthermore, H. pylori can inhibit the secretory response of mucous cells in vitro, indicating a potential deleterious effect on the quantity of this primary defense mechanism of the gastric mucosa (1).

Colonization of H. pylori in stomach

Urease expression and motility by flagella permit H. pylori to survive transiently in an acid environment and to colonize persistently the mucous layer (1). There are three essential factors for H. pylori to colonize the gastric mucosa: flagella, urease, and adhesins. (2) Firstly, H. pylori’s unique flagella in one end and its curved morphology cause screw-like movements, which may enable the organism to penetrate the mucin layer. The motility of H. pylori is increased when the viscosity of the media is increased in vitro and transverses a methyl glucose solution 10 times more efficiently than Escherichia coli, but the motility is pH dependent and impaired at a pH below 4. (2) its flagella are composed of flagellin and are surrounded by a membranous sheath containing LPS and protein generating an immune response. H. pylori-mediated reduction of mucus synthesis or secretion may also assist the bacterium in gaining access to the epithelium and persisting at this location (7). Secondly, urease is one of the most necessary enzymes in H. pylori pathogenesis because it maintains a pH-neutral microenvironment around the bacteria which is necessary for survival in the acidic stomach. It is well established that H. pylori grows best at neutral pH and fails to survive at a pH below 4.0 or above 8.2 in the absence of urea. Urease converts urea, of which there is an abundant supply in the stomach (from saliva and gastric juices), into bicarbonate and ammonia, which are strong bases. This creates a cloud of acid neutralizing chemicals around the H. pylori, protecting it from the acid in the stomach. (2, 5) Lastly, H. pylori adheres to mucin and binds specifically to gastric mucosa epithelial cells both in vivo and in vitro (2). The adherence allows the bacteria to anchor themselves to the epithelial layer, but bacteria that remain sttached to epithelial cells will eventually be swept away as these cells die and are exfoliated. Thus, a proportion of the H. pylori population exists in the nonadherent state. H. pylori must also contend with antibodies and phagocytic cells as the host mounts an immune response (7).