Helicobacter

Helicobacter pylori is a gram-negative bacterium that causes gastric infection. It is the most well known and clinically significant species of Helicobacter. Transmission is believed to occur by ingestion of contaminated food or water; therefore, a higher prevalence of infection is seen in areas with poor sanitation. Certain bacterial features contribute to the pathogenicity of H. pylori: urease production (allowing survival in an acidic environment), motility (permitting movement to the gastric epithelium), and several toxins (creating local damage and inflammation). Chronic infection with H. pylori can lead to peptic ulcer disease or even gastric cancer in severe cases.

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Classification

Gram-negative bacteria:
Most bacteria can be classified according to a lab procedure called Gram staining.
Bacteria with cell walls that have a thin layer of peptidoglycan do not retain the crystal violet stain utilized in Gram staining. These bacteria do, however, retain the safranin counterstain and thus appear as pinkish-red on the stain, making them gram negative. These bacteria can be further classified according to morphology (diplococci, curved rods, bacilli, and coccobacilli) and their ability to grow in the presence of oxygen (aerobic versus anaerobic). The bacteria can be more narrowly identified by growing them on specific media (triple sugar iron (TSI) agar) where their enzymes can be identified (urease, oxidase) and their ability to ferment lactose can be tested.
* Stains poorly on Gram stain
** Pleomorphic rod/coccobacillus
*** Require special transport media

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Characteristics

Features:

  • Stains:
    • Gram-negative
    • Detected with silver stain 
  • Morphology:
    • Motile rod
    • Curved shape
    • Contains multiple flagella
  • Growth and culture:
    • Microaerophilic
    • Complex growth requirements (special transport media required)
    • Oxidase-positive, catalase-positive
    • Urease-positive production: creates alkaline environment that permits survival of bacteria in acidic mucosa

Helicobacter genus contains about 35 species, with H. pylori being the most well known.

Electron micrograph of Helicobacter pylori possessing multiple flagella (negative staining)

Image: “Electron micrograph of helicobacter pylori” by Yutaka Tsutsumi, M.D. License: Public Domain

Pathogenesis

Transmission

  • Ubiquitous organism 
  • Humans are the primary reservoir.
  • Acquired by: 
    • Ingestion:
      • Oral–oral transmission: bacteria regurgitated with gastric content and temporarily colonize oral cavity
      • Fecal–oral transmission: contaminated food and water supplies (poor sanitation)
    • Person-to-person contact: clusters of infection noted in families
  • Prevalence of infection:
    • Low during childhood
    • 40%–50% in older adults
    • Highest in developing countries

Infection by Helicobacter pylori via ingestion of a pathogen results in gastric ulcers or gastritis.

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Pathogenic features of Helicobacter pylori

  • Urease-positive organism that produces ammonia:
    • Neutralizes gastric acid → hypochloridia → stimulates gastrin production → increased gastric acid → mucosal damage
    • Initial neutralization of gastric acid allows for mucosal colonization.
  • Multiple flagella allow for rapid penetration of the mucosa.
  • Contains mucinase and cytotoxins:
    •  Produces local tissue damage
    • Acts as chemoattractant and activates host inflammatory response 
  • Effects: gastritis, development of ulcer(s), gastric carcinoma and gastric MALT lymphomas

Pathogenic features of Helicobacter pylori

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Associated Diseases

Gastritis

  • Increased production of stomach acid or damage of the gastric mucosal barrier → irritate the sensitive stomach lining → gastritis
  • H. pylori infection is one of the most common etiologies. 
  • May be asymptomatic, or symptoms may include burning abdominal pain, dyspepsia, nausea, and vomiting 
  • Management of H. pylori infection: proton pump inhibitors with antibiotics

Gastric and duodenal ulcers

  • Two most common types of peptic ulcers:
    • Gastric ulcers:
      • Located in the stomach
      • Classically associated with pain that is worse when eating
    • Duodenal ulcers:
      • Located in the duodenum
      • Typically have improvement in the level of pain while eating, followed by worsening of pain after the conclusion of the meal. 
  • Most common etiologies include H. pylori infection and prolonged use of NSAIDs. 
  • Management: 
    • H. pylori eradication (antibiotics and proton pump inhibitors)
    • Eliminating risk factors

Gastric adenocarcinoma

  • Gastric cancer is the formation of malignant neoplasms of the stomach lining. 
  • Second most common cancer of the GI tract
  • Chronic H. pylori infection: associated with an increased risk of gastric adenocarcinoma

Iron deficiency anemia and vitamin B12 deficiency

In H. pylori infection:

  • ↓ Absorption of iron in the GI tract is observed, as uptake of iron requires an acidic environment. 
  • Chronic gastritis creates inflammatory damage to acid-producing cells → loss of acid production → reduced iron absorption
  • Ongoing inflammation likewise leads to loss of parietal cells from which intrinsic factor is produced. 
  • Without intrinsic factor, vitamin B12 deficiency develops.

References

  1. Jensen P. J., Feldman M. (2020). Acute and chronic gastritis due to Helicobacter pylori. Retrieved 20 April 2021, from https://www.uptodate.com/contents/acute-and-chronic-gastritis-due-to-helicobacter-pylori
  2. Kusters J. G., van Vliet A. H. M., Kuipers E. J. (2006). Pathogenesis of Helicobacter pylori infection. Clinical Microbiology Reviews 19:449–490.
  3. Riedel S., Hobden J. A., Miller S., et al. (Eds.). (2019). Jawetz, Melnick, & Adelberg’s Medical Microbiology, 28th ed. McGraw-Hill.
  4. Lamont, J. T., Feldman M. (2020). Bacteriology and epidemiology of Helicobacter pylori infection. Retrieved 20 April 2021, from https://www.uptodate.com/contents/bacteriology-and-epidemiology-of-helicobacter-pylori-infection

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