LONDON ¿ The bacterium Helicobacter pylori ¿ which commonly colonizes the stomach ¿ has assumed the role of the villain in many studies which implicated it in the development of peptic-ulcer disease and stomach cancer.

Its fortunes may have turned, however. A letter to the April 22 issue of Nature says this bacterium contains an antibacterial peptide. Its antibacterial activity, suggest the Swedish authors of the letter, may protect those people who have H. pylori in their stomachs from other infectious agents such as the bacterium that causes cholera.

Staffan Normark, professor of microbiology at the Microbiology and Tumour Biology Centre of the Karolinska Institute in Stockholm, Sweden, and senior author of the letter, told BioWorld International: ¿We know that there are many Helicobacters that don¿t cause any symptoms ¿ after all, most people who are colonized by H. pylori have no symptoms or disease. So, it might be the case that certain variants of H. pylori are more likely to be associated with disease than others. This is the case with Escherichia coli ¿ we all have E. coli as a normal part of our gut flora, but certain E. coli have attributes that make them pathogenic.¿

The study, by Katrin Putsep, Normark and colleagues, challenges, Normark said, the assumption that colonization of the stomach with H. pylori is inevitably undesirable. In developing countries where pathogens may be more widespread in food and the environment, H. pylori might confer benefits, he said, by stimulating mucosal immunity and by its antibacterial effect on other bacteria.

H. pylori was discovered in 1983. Since then, it has been shown that people who have it in their stomachs are more likely to develop peptic ulcers and stomach cancer. The decrease in incidence of these conditions seems to be linked to the decline in the prevalence of H. pylori infection.

¿On the other hand,¿ Normark added, ¿H. pylori is colonizing more than 3 billion people in the world and, in many developing countries, most people have it in their stomachs. So, you could argue that it is the most natural thing for humans to be colonized with. The question we wanted to answer was: If it is part of the normal stomach flora, does it have any potential benefits, especially to people living in developing countries who are heavily exposed to a lot of pathogens? If this is the case, then we need to be very careful before we start to eradicate this organism from humans.¿

One study had already shown, he said, that people colonized by H. pylori responded better to cholera vaccine than those who were not.

Normark and his colleagues made an extract of H. pylori, and were able to show that it had antibacterial activity.

H. pylori Sequence Similar to Cecropins

A member of the research team, Hans Boman, had already identified antibacterial peptides made by insects, called cecropins. So, the researchers examined the genome of H. pylori, to see if it contained any sequences similar to those present in the insect genes which coded for the cecropins. They were in luck. They found that the amino terminus of the ribosomal protein L1 (RpL1) of H. pylori had a sequence very similar to that of the cecropins.

Normark said: ¿We then synthesized peptides based on this sequence, and found that these peptides also behaved very much like cecropins, and had killing activity against E. coli and bacillus bacteria.¿ Further studies showed that H. pylori itself was resistant to both the synthetic peptides and to cecropins.

The researchers then tried to find out if the antibacterial activity present in the original extract was due to RpL1. They separated the peptides present in the extract and tested each one for antibacterial activity, and also checked whether the peptide present was, in fact, the amino terminus of RpL1. ¿Our results showed,¿ Normark added, ¿that the activity emanated from the degradation of RpL1.¿

One theory, put forward by Suhas Phadnis in the U.S., is that a proportion of the H. pylori colonizing the stomach undergoes lysis all the time. Normark pointed out that RpL1, as it is a ribosomal protein, is not normally secreted. ¿For this protein to play a role, this would suggest that Phadnis¿ theory is correct,¿ he said. ¿H. pylori would release cytosolic protein while growing in the stomach, including this peptide with antibacterial activity.¿ He emphasized that this is only speculation, and remains to be demonstrated.

Studies Under Way To Prove Theory

The question the team now wants to answer is whether H. pylori can indeed prevent growth of other bacteria ¿ for example, whether it can prevent colonization of the upper part of the intestine by cholera bacteria. It has already embarked on an experiment with germ-free mice, which they are colonizing with H. pylori and then challenging with other infectious agents.

Normark described the finding as ¿interesting and intriguing,¿ not least because it may shed light on the evolution of the various antibacterial peptides. He and his colleagues write in Nature: ¿Our data are also consistent with the idea that cecropins have evolved from an early rpl1 gene in a prokaryote that passed from being an intracellular parasite to a symbiont, ending up as an organelle. When the rpl1 gene moved from the organelle to the host nucleus, a duplicated sequence could have begun to evolve towards a specialized antimicrobial peptide.¿

Peptides such as that identified in this study also have interesting potential to be developed as new antibiotics, Normark concluded. ¿If they are part of our natural defense system, we could also think about developing treatments that increase their production.¿ n