With food safety the order of the day for the produce industry, the availability of phage-based products that help prevent foodborne illnesses such as Listeria monocytogenes and E.coli O157:H7 is a positive sign. Salmonella-fighting solutions are in the pipeline too for an industry that is currently focused on food processing, mainly in meat, fish and cheese, but with applications that have been seen for fresh-cut fruit and vegetables. At www.freshfruitportal.com we speak with two phage product companies, one in the U.S. and the other in the Netherlands, about how technology utilizing these ancient organisms could be the future for supermarket produce aisles, and perhaps even consumers. 

The fatal outbreaks of E.coli in Germany and Listeria in the U.S. last year would be etched into the minds of every respectable produce industry professional around the globe.

Looking just from a financial perspective, Jensen Farms - the source of the 2011 canteloupe scare - filed for bankruptcy in May.

Traceability helps reduce the probability of these events but it can only go so far. There can never be any quick fix when it comes to food health concerns, but investigation has been underway and continues to look for ways to save more lives through prevention.

Baltimore-based Intralytics chief scientist Dr. Alexander Sulakvelidze was drawn into the field of foodborne illness prevention through an "innocuous conversation" with infectious disease expert Dr Glenn Morris, asking him why phage treatment hadn't worked with a patient.

"I was a recent arrival from Georgia in Eastern Europe where bacteria phages were and are still used to treat bacterial infections, but it was the first Glenn had heard of it," said Sulakvelidze.

Intralytics was then founded in 1998 with the aim of developing treatments with phages in the medical field, the most abundant microorganisms on the planet that serve the function of destroying bacteria. However, it soon became apparent the concept was "too novel" for the U.S. medical community and it would be less costly to make products for the food industry.

"We were successful as the first company to develop and receive FDA (Food and Drug Administration) approval for a phage-based product to treat foodborne disease with ListShield in 2006, which is used to treat Listeria monocytogenes," he said.

"Just recently we have gained our second approval from the FDA for EcoShield which is an active agent against E.coli O157:H7; the disease is a huge problem, particularly for ground beef but also for fruits and vegetables.

"We have also just completed development of our third product which is targeted against salmonella, and we have submitted that to the FDA and expect approval to be granted hopefully within a few months, and certainly this year."

He said the products work as sprays, developed by selecting the most suitable phages from the environment and then confirming that they kill the targeted disease bacteria.

"This is the most environmentally friendly product out there for this as it doesn’t impact on taste, appearance, shelf life, anything like that – it’s as if you were using spring water, but if the food happens to be contaminated by foodborne disease it will kill the disease bacteria.

"At this point the products are being used by food manufacturing companies but eventually we expect they will be used in supermarkets and potentially by people in their own homes.

"For example you might have a salad and you want to make sure it is safe, so you spray a cocktail of our products to eliminate or significantly reduce the potential for foodborne disease."

What are phages?

Dirk de Meester is the business development director of Dutch company Micreos B.V., a company that also sells a phage-based treatment against Listeria monocytogenes called Listex. He said phages could be understood by their Greek meaning, 'bacteria killer'.

"Every 48 hours 50% of the bacteria population is killed by phages, which are the most abundant microorganism in the planet, outnumbering bacteria 10 to one, and that’s reflected in that you can find up to a billion phages in a milliliter of seawater," said the Wageningen-based exec.

"They’re common residents in intestinal tracts and anywhere where you have bacteria – they are typically one hundred times smaller than bacteria, they’re harmless to humans, animals and plants and they affect only bacteria.

De Meester said the first stage of the lytic cycle is absorption where the phage recognizes receptors on the cell wall, while the second step is infection whereby the DNA of the phage sucks into the cell wall.

"It then hijacks the metabolism of the cell and replicates within the cell, before you have the maturation stage and the progenies escape."

This is what we aim to do with our products. From an application point of view as soon as the DNA is in the host cell, this is a dead cell; it will never be able to multiply or divide again."

Product applications

Listex is used in more than 30 countries that are mostly in North America and Europe, but also for fish exporters in Asia and some food processors in South Africa. It is approved by the FDA and Health Canada for use as a processing aid, while the same approval is expected for Australia and New Zealand in July.

De Meester said the main focus has been with meat, fish and chees but the company has done work on lettuce, cucumbers, melons, peas, tomatoes, parsley, cabbage.

"Once you cut a ready to eat convenience product, you cut into the leaf or into the vegetable and the rich nutrients and juices are freed, so they don't have their natural protection any more, and that is a point of growth for bacteria - they love that," he said.

"We've seen very strong reductions of these types of problems. It involves rinsing with phage, just spraying onto conveyors where product is going over the line just as a microbial treatment before going into the bag."

He said the company was also working on projects to apply phages in new ways to avoid cross-contamination of bacteria, which could have implications for retailers.

"It is very interesting that bacteria phages don’t react away in the presence of proteins like chemicals, such as chloride or hydrogen peroxide, and that means once you spray onto a surface of vegetables in a supermarket, the phages linger there, and once people with their hands they pick up the fruit, smell it and put it back, they get phage on their hands and they don’t spread it.

"Also, the misting systems used to keep fruit fresh so that it doesn’t dry out, can actually be combined with phages, which gives a kind of natural protection while the people are handling the fruit.

"We also work with stainless steel food contact surfaces which reduced the level of bacteria significantly; even as a treatment during production you can ensure that food contact surfaces do not lead to cross-contamination; it's a very interesting concept."

He added the products were best used in a preventative way, cautioning that the level of success depended on how much was used.

"It always depends on the dose; we always try to use a preventative approach as you get a two or three log reduction, but once you have loads of 10 to the fourth or sixth, then with a two or three log reduction you will always have remaining bacteria."

The future of phage

Sulakvelidze said these types of products had good potential, while his company could likely pay off its cost of investment over five years, but the biggest challenge was psychological with phages out of fashion in medicine for the last half-century.

"Phages were used in the U.S. in the 20s and 30s for medical treatment, but when antibiotics came in phages went out; however in the Soviet countries at the time phages continued to be used in addition to antibiotics, and that’s how it still is today in many of these countries.

"The simple reason why they've been forgotten by so many is that before antibiotics you might have had someone with a bacterial infection but you didn't know what it was, so you didn't know which phage to apply and the one you chose might not have worked.

"Antibiotics on the other hand are stronger and have a wider scope. But today this is being revisited because the overuse of antibiotics has created higher drug resistance, while on the other hand diagnostic approaches are more precise and faster now, so you can choose the right phage to use."

He said the "average Joe on the street" wouldn't know what a phage was, even though they have been used for thousands of years by people, so it would take time for the psychology to kick in.

De Meester said phages were a "logical candidate" to take care of pathogens in food, given they have co-evolved with bacteria for billions of years.

"The more food we need to produce and the more pressure we put on the system, the more you’re going to be vulnerable for pathogenic strains and emerging strains and outbreaks.

"If you’re making products which are convenience products then as soon as you’re putting your knife into that product, then the clock starts to tick, and phages can be a valuable tool to make sure that the dangerous pathogens that grow at refrigeration temperature don’t have a chance."

Click here for an informative Intralytics video about phages.

www.freshfruitportal.com