The human pathogenic bacterium Helicobacter pylori and its impact on human health

Utkarsh verma

AnxietyStressIrregular food habitsExam phobia

Gastritis

Acid blocker; AntacidTemporary Relief

Relapse

Normal beliefs regarding gastritis

Acid secretion

R. Warren B. Marshall

Warren and Marshall revolutionised the concept of gastroduodenal diseases

Robin observed the presence of small Curved bacteriaColonizing lower partOf the stomach

Marshall later Initiated a study With 100 patients &Confirmed the Presence of the Bacteria in the stomach

Marshall succeeded in cultivating the bacteria from the biopsies. Together, they found that the organism was present in almost all patients with gastric inflammation, duodenal and gastric ulcer(1982).

The Nobel Prize in Physiology or Medicine for 2005

The cultured microorganism should cause disease when introduced into a healthy organism

Barry Marshal had to inoculate himself with H. pylori to show that it causes infection

1843-1910

The Bacterium

Flagella

AdhesinH. pylori

Places of Infection in the stomach

H. pylori infects the lower part of the stomach, antrum

Duodenum

Corpus

Pylorus Antrum

H. pyloriLow pH

Inflammation

H. pylori causes inflammation of the gastric mucosa (gastritis)

Ammonia causes damage to the cells

Inflammation initial response of the body to harmful stimuli and is achieved by the increased movement of leucocytes from the blood into the injured tissues

Ulcer (schematic)

Inflammation

Duodenal ulcer

Gastric ulcer

Bleeding ulcer

Gastric inflammation may lead to duodenal ulcer followed by bleeding ulcer

Ulcer (real)

Urease

CO2 + NH3

Ammonia NeutralizesAcidicSurroundings

13C Urea Solution Ingested

Lungs

13CO2 absorbedin blood

13CO2 detected

Bacterial survival and urea breath test for detectionDiagnosis

Noninvasive

Invasive: Endoscopy Biopsy Culture

Treatment

Amoxycillin, Clarithromycin, Tetracycline and metronidazole.

Antibiotics

Ranitidine, Cimetidine, Famotidine, Omprazole, Pantoprazole and Lansoprazole

Acid lowering drugs

Combination of the above two for two weeks is the best strategy

Vaccination: Not available yet

However, there are incidences of drug resistant strains

Malignancies associated with Helicobacter pylori infection

H. pylori infection in the stomach

Prolonged and widespread inflammation and gastritis

Malignant change leads to stomach cancer

Number two in cancer deaths

??CagA protein

Uncontrolled growth of cells

Key Questions

How H. pylori cause cancer? What are the key determinants?

Can we design new drugs? What will be the target?

Can we design new vaccine? What will be the antigen?

Genomics and Proteomics

Molecular Cell Biology Immunization

Genome analysis,Gene expressionProfiling,Functional genomics,Novel proteincharacterization

DNA repair,DNA replication,Transcription,Cellular metabolism

Vaccines,Recombinant Vaccines,DNA vaccines

Research In Progress

Gyrase

Helicase

Helicase and gyrase action

LeadingStrand

Lagging Strand

Helicase unwinds DNA

GyraseRelieves tension

We Study H. Pylori DnaB Helicase

ATP Hydrolysis: Release of Energy

Breaking Hydrogen bonds using ATP

ELECTRON MICROSCOPIC OBSERVATION OF HELICASES

3-D structure of a protein

X-RAY Diffraction of Protein Crystals yield 3-D Structure

Sharma A and Dhar SK. (2005) Helicobacter pylori infection: Diseases and Cure: A molecular approach in Microbes for Human Health. I. K. International Publication.

Website: http://www.helico.com/

Further reading and information

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