Helicobacter pylori

Helicobacter pylori secretes urease to maintain a basic/neutral environment. Lophotrichous tufted flagella, powered by a proton gradient, give it motility. Helicobacter pylori is extracellular and does not need to be intracellular to replicate. They have a tuft at one end, and this is mediated by that they are encased in a membrane. The structure of VacA is like a flower petal such that it might almost form a pore but it is unclear what it does with pathogenicity.

1881 & 1893: Spiral organisms found in stomach contents of dogs and other mammals
1938: Spiral organisms first described in human gastric mucosa
1975: First attempts to culture gastric bacteria
1982: Helicobacter pylori cultured and shown to cause ulcers

Helicobacter pylori is associated with gastritis, duodenal and gastric ulcers and gastric adenocarcinomas. Gastric adenocarcinomas are the 14^th leading cause of death in the world, and are believed to be the 8^th leading cause by 2010. This is largely because infection in the lumen of the stomach is not accessible to immunocytes and macrophages.

90% of duodenal ulcers and 70% of gastric ulcers are Helicobacter pylori positive. Presence of gastritis is a risk factor for duodenal ulces and ulcer relapse. Cure of Helicobacter pylori infection leads to a dramatic reduction in ulcer relapse rate. Addition of antibiotics to acid suppressive therapy increases speed of healing of acute ulcers.

Helicobacter pylori and Human Ulcer Diseases

Transmission:
Ancient association with humans. Believed to be present in human stomachs before. Human migration started ~100,000 years ago. Overlap between genetically distinct H. pylori and human populations.

Transmission

Developing Countries

80% population colonized
Colonization during childhood
Parent-child transmission (genotyping)
Strains persist and re-infection rare
Very low rate of ulcers!

Industrialized Nations

20-50% population colonized
Colonization later in life
Transmission between spouses rare
Rare childhood infection rate (<20%)

Colonizaiton → immunomodulation → host remodeling → symptoms

1. Oral ingestion
2. Transit of gastric environment
a) Adult stomach pH ~ 1-2
b) Infection occurs in early childhood, higher stomach pH
3. Penetrating gastric mucus
a) Thick (viscous), and sloughing action
4. Attachment
a) Allows bacteria to persist in stomach
5. No competition for H. pylori once established on the mucosal
surface
Route of infectionRoute of infection

Interesting genes of Interesting genes of Helicobacter pyloriHelicobacter pylori