Helicobacter pylori
Monday, November 5th, 2007
Here is tale of brave microbiologists on the trail of the most fabulous beast in the prokaryotic kingdom. The saga of Helicobacter pylori is one to rival the early feats of Pasteur, Koch and Beijerinck.
Helicobacter pylori is a helical Gram-negative bacterium which infects the stomach and duodenum. Many people who are infected with this microbe do not show any symptoms of disease, but in other cases a lifetime of infection can lead to peptic ulcers, gastritis and perhaps stomach cancer.
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In the 19th century, German and Italian scientists described helical bacteria in the lining of the stomach of humans and dogs, but because they could not be grown in culture, they were eventually forgotten. These organisms were rediscovered at the end of the 1970s by Australian doctors Robin Warren and Barry Marshall. In a controversial paper, Warren and Marshall argued that most stomach ulcers and gastritis were caused by infection by this bacterium and not by stress or spicy food as had been assumed previously (Unidentified curved bacilli in the stomach patients with gastritis and peptic ulceration. Lancet 1984 8390: 1311-1315). The idea that this bacterium could cause stomach ulcers was met with a great deal of scepticism. Eventually, Barry Marshall deliberately swallowed a culture of the bacterium (don’t try this at home). A week later, he began to suffer acute symptoms of gastritis, and stomach biopsies revealed that he had become infected with H. pylori and showed severe acute gastritis. Marshall wrote:
Becoming increasingly frustrated with the negative response to my work I realized I had to have an animal model and decided to use myself. Much has been written about the episode and I certainly had no idea it would become as important as it has. I didn’t actually expect to become as ill as I did. I didn’t discuss it with the ethics committee at the hospital. More significantly, I didn’t discuss it in detail with Adrienne [his wife]. She was already convinced about the risk of these bacteria and I knew I would never get her approval. This was one of those occasions when it would be easier to get forgiveness than permission. I was taken by surprise by the severity of the infection. When I came home with my biopsy results showing colonization and classic histological damage to my stomach, Adrienne suggested it was time to treat myself. I had a successful infection, I had proved my point.
Fortunately, Marshall was able to cure himself with a course of multiple antibiotics, which is now the standard therapy for Helicobacter infection. In spite of this dumb stunt, the 2005 Nobel Prize in Physiology or Medicine was awarded to Marshall and Warren “for their discovery of the bacterium Helicobacter pylori and its role in gastritis and peptic ulcer disease”.
Unfortunately, an increasing number of infected individuals are found to harbour antibiotic-resistant strains of Helicobacter. This results in initial treatment failure and requires additional rounds of antibiotic therapy or alternative strategies such as a quadruple therapy (treatment for four antibiotics).
Helicobacter species are one of the few known microorganisms which can not only survive but thrive in the highly acidic environment of the stomach. The helical shape of the organism may help penetration of and motility in the mucus gel layer which protects the body from stomach acids. In addition, the bacteria produce a large amount of urease, an enzyme that breaks down urea into ammonia and carbon dioxide and forms a protective alkaline layer around them. This discovery enabled Marshall to develop a non-invasive breath test: patients swallow a small amount of urea labeled with a carbon isotope, and if H. pylori are present, the urea is broken down to release mildly radioactive carbon dioxide in the breath. As this is much more fun than having a stomach biopsy, this has become a common way of diagnosing H. pylori infection.
So that’s the saga of Helicobacter pylori. Because we could not grow it in the laboratory, we pretended it did not exist. It took a man with a strong stomach to show us the error of ignoring this unusual organism.
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