By Sean Henahan, Access Excellence 

Graphic: Helicobacter pylori, a micro-aerophilic, Gram-negative, spiral, flagellated organism

The research also represents a another important step ahead from the state of knowledge only a few short years ago when ulcer patients were told to avoid stress and drink milk, with surgery the last resort. Fifteen years ago, when gastroenterologist Barry Marshall first suggested that H. pylori bacteria caused ulcers, the medical profession was almost uniformly skeptical. However, subsequent research by Marshall and others has shown that not only is the bacteria responsible for a majority of ulcers, eradicating it with common antibiotics usually leads to a cure. 

Researchers at the Institute for Genomic Research disassembled the H. pylori genome into pieces and then sequenced each piece. Computers then were used to determine the sequence of the genome. The final result, a genomic map of the 1.6 million base pairs in H. pylori's circular chromosome (1590 genes) has now been published and is available free to all researchers. 

"This is a genome that has something for everyone -- clinicians, sociologists, epidemiologists, biochemists, ecologists, molecular biologists, immunologists and, last mentioned but hardly least interested, evolutionary biologists,"  noted Dr. Russell R. Doolittle of the University of California at San Diego, in a commentary. 

One of the first benefits of the genome sequencing has been an enhanced understanding of how the bacteria colonize the stomach and how they survive in the very acidic conditions of the gut. For one thing, the bacteria appears to have a unique mechanism for evading the human immune response. Another new finding shows that the bacteria is able to get a foothold in the stomach by releasing factors that suppress acid production locally. The organism also survives in acid conditions by establishing a positive inside-membrane potential in low pH. 

Sequence analyses also indicate that H. pylori has well-developed systems for motility, for scavenging iron, and for DNA restriction and modification, the researchers report. While much remains to be explored, the researchers also identified many putative adhesins, lipoproteins and other outer membrane proteins of the organism. 

"The determination of the entire gene complement of H. pylori will allow the identification of novel drug targets and the development of new antibiotics and an effective vaccine," said Dr. J. Craig Venter, director of the Institute of Genomic Research. 

BACKGROUND 

Helicobacter pylori is a spiral shaped bacterium that lives in the stomach and duodenum. The inside of the stomach is bathed in about half a gallon of gastric juice every day. The stomach is protected from its own gastric juice by a thick layer of mucus that covers the stomach lining. Helicobacter pylori takes advantage of this protection by living in the mucus lining. Once H. pylori is established it counteracts the stomach acid that does reach it with an enzyme it possesses called urease. Urease converts urea in the stomach into bicarbonate and ammonia, in effect creating its own antacid bath. 

H. pylori is now recognized as one of the most common pathogens afflicting humans. In the developed worlds H.pylori is believed to affect about 20% of persons below the age of 40 years, and 50% of those above the age of 60 years. In many developing countries a majority of adults are believed to be infected with H. pylori, along with a growing number of children. While questions about the route of transmission remain, both oral and fecal routes have been implicated in the spread of the organism. 

Now that  H.pylori's role in ulcer formation has become accepted, physicians are often able to resolve ulcer symptoms with a short course of  antibiotics. The organism has also been implicated in some gastric cancers, a further incentive to develop a vaccine. 

The research was published in the August 7, 1997 issue of the journal  Nature.