Scientists long suspected that Helicobacter pylori's ability to survive in the hostile acidic environment of the stomach owed to its corkscrew shape - but not why.
Credit: Massachusetts Institute of Technology
SYDNEY: The helical shape of the bacterium Helicobacter pylori, which causes many ulcers and gastric cancer, is critical in its ability to colonise the stomach.
Scientists have suspected that H. pylori’s ability to survive in the hostile acidic environment of the stomach owed to its corkscrew shape - but not why.
Now researchers at the Fred Hutchinson Cancer Research Centre in Seattle, Washington, have found proof that the bacterium’s shape allows it to survive amid gastric juices and to infect the stomach.
“By understanding how the bug colonises the stomach, we can think about targeting therapy to prevent infection in the first place,” said microbiologist Nina Salama, one of the authors of the new study appearing in the journal Cell.
“H. pylori lives in such an unusual environment [the stomach], which people for a long time thought was sterile,” said Salama. And until the early 1980s, no one suspected that a bug could cause stomach ulcers and gastritis.
Hardy bacteria
Then Australian scientists Barry J. Marshall and Robin Warren discovered the hardy bacteria in samples isolated from the human stomach, and found that it was in fact the cause of these ailments. The work earned the duo the 2005 Nobel Prize in Physiology or Medicine.
“H. pylori uses a combination of strategies to set up shop in the stomach,” said Salama. An enzyme called urease protects it from the stomach acid. Then it uses its flagellum to bore into the mucous layer, which buffers the cells lining the stomach from acid.
The H. pylori bacteria reside in the stomachs of about half of all humans, but have co-evolved so that in most people they cause little problem.
Still, more than 10% of those infected can develop serious disease, and H. pylori is the only bacterium listed as a carcinogen by the World Health Organisation.
The bacteria will not infect successfully if it lacks precisely the right shape, said Salama and colleagues. They identified four proteins responsible for H. pylori’s helix, and cultured mutant strains in which some of those were missing.
Mutant forms
They reported that the mutant forms took on different shapes, from rods to crescents, and that the malformed bacteria failed to infect the stomachs of the mice in the experiment.
A mesh structure encapsulates the cell, and the proteins that determine its shape break certain peptide bonds – in essence, snipping pieces of that mesh. That allows a rod-shaped cell to curl up into a spiral.
“There is a real possibility of designing or screening for inhibitors that block this enzymatic function,” denying the bacteria of their critical adaptation, said Salama.
At present, antibiotics can treat H. pylori infections, but drug resistance is making it increasingly difficult to eradicate. There are also no vaccines.
“The identification of unique target proteins in bacteria like Helicobacter raises the possibility that highly specific antibiotics might be developed,” said Richard Strugnell, a microbiologist at the University of Melbourne.
Strugnell said that the link between the bacteria’s curved structure and their function could be common in mucous-residing bacteria. “[This] might lead to the development of an antibiotic that targeted all oddly shaped organisms that shared similar enzymes to the proteins in Helicobacter,” he said.
Other bacteria with these proteins include those that cause cholera and gastroenteritis, the leading cause of bacterial diarrhoea in developed countries.
