Adding viruses to your food--on purpose

I blogged previously on the potential of bacteriophage, viruses that infect--and often kill--bacteria, in treating bacterial infections that are resistant to our current antibiotics. This is an area that's really just opening up, and while there is a lot of promise, there are also a significant number of obstacles. One thing I didn't mention, however, was the potential of bacteriophage for other public health measures--such as a bacteriocidal food additive.

(More below)

A mix of bacteria-killing viruses can be safely sprayed on cold cuts, hot dogs and sausages to combat common microbes that kill hundreds of people a year, federal health officials said Friday in granting the first-ever approval of viruses as a food additive.

The special viruses called bacteriophages are meant to kill strains of the Listeria monocytogenes bacterium, the Food and Drug Administration said in declaring it safe to use on ready-to-eat meats prior to their packaging.

Listeria isn't necessarily the most common bacterial contaminant of food, but it's the most insidious. It can replicate even at low temperatures (meaning that even with refrigeration, Listeria-contaminated food can become more deadly over time). This is especially a problem for foods like cold cuts, which generally aren't heated again before they're served--meaning all those bacteria go right into the stomach and digestive system with very little to stand in their way. And Listeria can kill. The bacteria are especially deadly to those who have compromised immune systems (such as the elderly or people on immunosuppressive drugs), and as I blogged about here, they can also cause miscarriage in pregnant women. (This is why this group is often advised to stay away from cold cuts as a rule of thumb).

The article mentions that similar sprays are in the works to combat E. coli, another common cause of food poisoning. What they don't mention, however, is whether these bacteriophage are broad-spectrum. Some of them are quite picky about the bacteria they infect, killing not only specific species of bacteria, but even specific strains within a species. (For example, a phage may infect and kill E. coli serotype O157:H7, but may not even infect E. coli of different serotypes). I assume this has been worked out with regard to Listeria, but no mention is given to it in the short article. All in all, a promising development, and one that has the potential to bring bacteriophage research into the limelight.

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I could foresee this being quite abused.
Maybe the spray should be only given out via prescription, ie to people that are immunocompromised. I can just imagine some idiot misting his fridge with this. As if bacteria weren't drug resistant enough.

This is sooooo coool!!!! I am going to my deli and order a virus and bologna sandwich. This is a great bit of science impacting the public, that my class will here of it tomorrow.
Thanks T

Indeed, bacteriophage are very interesting. The possibility of bacteriophage therapy as an alternative to antibiotics is quite intriguing, especailly given the current situation with the spread of multi-resistances. I have a colleague who works on phages and who tells me that in the ex-USSR countries, phage therapies are being used on patients with infections that do not respond to antibiotics. Apparently they were already being pioneered at the beginning of the century but were dropped for the more easily administered penicillin and subsequent antibiotics. Funny that we might be doing a 'Back to the Future' flip.

I would be a bit wary of actually spreading them on my food, though; phages are a great agent of lateral gene transfer. It would be counter-productive if they happened to mediate a recombination event leading to a superbug. But then I maybe that's just my paranoia talking. That said, early 20th century microbiologist Felix d'Herelle was already advocating fighting bacterial infections with phage preparations ingested with food (kind of like today's yogurts enriched with lactic bacteria, I suppose). I'm sure he'd be thrilled to see this new development... approval by the FDA! Quite a step forward, I suppose.

The question of specificity is at the same time a good thing and a bad thing. It may be problematic if the "bad bug" you're trying to get at is not sensitive to available phages, but it could avoid wiping out gut flora as 'collateral damage' like antibiotics tend to do. One example of phage specificity being useful in medical science is anthrax... B. anthracis is sensitive to phage gamma and this has been used as a diagnostic criterium. Maybe it could be turned into an anti-anthrax preventative. (I don't know, this is just me shooting off the top of my head - probably been thought of, deemed stupid, passed over)

This is very cool and could be a great addition to current antibiotics.

I wonder though how likely gene transfer is and I think it is definitly something to seriously consider. Lactic bacteria are natural to our guts to establish a balance so I think it is less likely for them to be problematic but how much is known on how the phages will behave in the gut especially in high concentrations. Any thoughts on the overuse of phage therapy or links to more info on the possibility of gene transfer?

Lateral gene transfer is a problem between strains of the same species, ie high-virulence E. coli and low-virulence E. coli. However, if the phage is strain specific, it isn't that big of a concern. Bacteria develop resistance to phage by utilizing restriction enzymes that target specific palindromic sequences of non-methylated DNA. Since phage DNA is foreign it hasn't been methylated as a part of normal DNA replication and is targeted. Phage can circumvent this by entering the lysogenic cycle where they insert their genome into the host bacterium genome. When conditions are favorable, usually stressful, the phage extracts its genome and begins replication. Since it has probably been in the host genome for a few rounds of replication, it is now methylatd and can avoid destruction by restriction enzymes.

Plus, Listeria monocytogenes isn't exactly resident gut flora, so the phage used shouldn't have targets inside the body. That's an issue for E. coli, however, depending on the strains they'll be targeting and as Zach notes, how specific they are.

I forgot to mention that not all phage are capable of lateral gene transfer. Most transducing phage contain double-stranded DNA. single-stranded DNA or RNA phages can't package double-stranded DNA so they aren't a problem. A double-stranded RNA phage could hold double-stranded DNA, but I don't think that the packaging system would allow it to occur. You also have to look at the size of the phage's genome. If it is small, there won't be too much concern about transduction as only parts of genes or only one gene of a multi-gene product will be transduced. Another complicating factor is that most transduction that is a concern occurs with the lysogenic cycle. Phage that undergo lysogeny insert into the host genome in a specific spot. When the phage genome is removed out of the host genome it sometimes takes too much DNA and a host gene is transferred as well. As long as this gene isn't part of a virulence factor, there is no concern with transduction. The random packaging of host genome pieces from lytic cycle action isn't usually a concern as it is rare to find whole functional genes.

Thanks for the explanation Zach, it helps a lot. I am going to read up on th lysogenic cycle as I am not clear on how that works but it definitly suggests risks are minimal. It sounds like a very promising area for further research.