Countless bacteria romp around in our food. Some of them fulfil a useful purpose in the production of fermented food products by acting as a sort of preservative, for instance.They can also prevent the spread of mycotoxins. On the other hand, cheese, salads or sausages are a paradise for all kinds of dangerous microbes. Enterococci, staphylococci or salmonellae cause illness. A notorious example of this in Switzerland was the case of "Vacherin Mont d’or“. Just over 20 years ago 122 people came down with listeriosis, some of whom even died as a consequence. The cause of the infection was listeria–a dangerous bacterium that had nested itself into the vacherin, a soft cheese made from raw (unpasteurized) milk.

Listeria continue to be a hot topic. 46 cases have occurred in Switzerland alone over the past twelve months. These bacteria are only transmitted via contaminated food sources, for the main part via food produced for raw consumption, such as milk products, sausages, salads or cream desserts. Preprepared dishes figure in the daily lives of growing numbers of people. The extent of the demand for convenience food is matched by the interest and efforts of researchers and the industry to develop reliable methods to ensure that these uninvited micro-guests don't get into our meals.

Millions of viruses

"My enemy's enemy is my friend", says Professor Martin Loessner from the ETH Institute of Food Science and Nutrition (1) and counts on the deployment of a natural enemy to fight bacteria in foodstuff. These troops are called bacteriophages, or phages for short. Phages are viruses, millions of them are to be found in both fresh and salt water. "In just a millilitre of water–taken, for example, out of the Limmat–there are at least 10,000 bacteriophages," says the food microbiologist. These so-called "bacteria eaters" have two decisive advantages: while doing no harm to animal cells, specifically selected bacteriophages precisely target dangerous microbes. The latter advantage is an important difference compared to the way antibiotics work, because these also attack useful bacteria.

With its appendices phages can only dock on the surface of a bacterium that has the appropriate receptors. Once docked, the phage parasitizes the host by infecting it with its own DNA, thus forcing the bacterium to reproduce about a hundred new phages. These phages then produce enzymes that break down the walls of the cell, resulting in the death of the host. For his research Loessner isolated the specific enzyme from those listeria phage that produce the bacteriophages and transferred it, in a pure form, onto the surface of food, for example a soft cheese (2).

The method of using bacteria's natural enemies to destroy them is far from new. Already 80 years ago efforts were undertaken to treat bacterial infections with bacteriophages. In the end, such treatment was driven out by the advent of antibiotics. In 1959 the World Health Organisation (WHO) concluded that, thanks to the successful development of antibiotics, there was no longer any need to continue with research on bacteriophages.

New solutions, old methods

So research on bacteriophages only continued to be carried out in the East European countries–such as the former Soviet Union, for example. Loessner says that where it was still done, one of the main reasons was lack of funds. "The financial means to adapt to and adopt new research methods was lacking." A situation that can almost be viewed as propitious today. Because bacteria are becoming increasingly resistant to antibiotica. Science is looking for new solutions and, for once, has returned to old methods. Exchange of specialist knowledge and experience plays an important role in this approach.

The use of genetically optimised "anti-listeria lactococci" for the production of Camembert can prevent this soft cheese from contamination with dangerous microbes. Picture: Martin Loessner. large

"A high level of know-how has been preserved in bacteriophage research in these countries over the past thirty or forty years that has attracted the interest of many companies in the West, above all in the USA," explains Loesser. To ensure against scientists being "taken to the cleaners" many of them work together with foundations and process their knowledge themselves. There was a scientific exchange with "western" scientists but the way science has been conducted in the former communist countries of East Europe for the past decades did not measure up to today's standards in food science, he adds. "The most serious omission was that regular controls were lacking." He himself had no direct scientific contacts with scientists in the former Soviet Union.

Race to arms

Even though Loessner is counting on phages to combat listeria he doesn't see this as a panacea. It was entirely plausible to imagine that bacteria could become restistant to phages. "An estimated 10 to the power of 30 bacteriophages exist on our planet. Faced with this multitude bacteria wouldn't have survived unless they had developed a certain resistance," as Loessner goes on to explain. His work can be compared to an arms race, a competition to find the best weapon. Moreover, treatment with phages was not something that can be prescribed over long periods, nor was it suitable for preventative treatment, as a huge number of viruses would be needed to provide effective immunity.

This has caused Loessner some problems in the development of his method. What he did was to introduce the genetic information for the enzymes that bacteriophages use to kill bacteria into lactic acid bacteria. These enzymes can then be isolated and put into foodstuff. For the food industry this would be an ideal solution. However, the period that the enzymes remain effective was limited and they were expensive to produce, says Loessner. These problems could be overcome if one were to introduce the genetically modified lactic acid bacteria directly into the target food, (instead of into the isolated enzymes), for example in cheese production.

Big provisos

However, the food industry has a great number of provisos when it comes to the use of genetic technology. "At the moment our work has a purely experimental status," says Loessner. Nothing was yet known of possible negative consequences on human beings of genetically optimised bacteria, such as allergic reactions, for example. "Such investigations are very complex and extremely expensive. Trials would need the interest and the financial support of a commercial partner," says the food microbiologist. So far, this is not the case. Nevertheless, the future looks promising. "We have a lot of tools, namely bacteriophages, at our disposal and we will carry on with our research," he says. With newly discovered old research measures like the bacteriophages, perhaps combined with modern genetic technology, he would also like to put a spanner in the works not only of listeria but of other dangerous microbes. It would also be possible to isolate phage enzymes to combat clostridia, staphylococci and bacilli. Intensive research is also on going in measures to fight salmonella, a well-known "enemy" in food microbiology, which also makes use of phages.