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How People Are Fighting Back

Part II

An interesting partial solution to this problem involves using certain types of viruses which attack bacteria, called bacteriophage.

Bacteriophage and bacteriophage therapy has been known about for a century. However the simultaneous discovery of antibiotics, along with a few poorly performed initial experiments that misunderstood just how specific phage are prevented their therapeutic use in the west. The Soviet Union had a facility in Soviet Georgia (George Eliava Institute) since the beginning of the 20th century which produced phage for the Soviet military. With the breakup of the Soviet Union, Eliava floundered, though it is currently working to find new markets and develop new treatments. It has recently set up shop in Tijuana, Mexico to serve the American market.

At this point, bacteriophage have strong potential for treating topical and gastro-intestinal infections as well as cleaning food , operating rooms, and certain crops and livestock. They also have potential for helping reduce traveler’s diarrhea. (It’s been speculated that part of the reason that travelers get sick from local water while natives don’t is because of the bacteriophage that lives in the intestines of the natives.)

While it would require a large cocktail of different phages to even begin to replicate the broad-spectrum nature of antibiotics (Eliava has used such cocktails), phage and antibiotics could be used simultaneously with no bad interaction. And because phage doesn’t have many of the problems associated with antibiotics, phage wouldn’t have to require a prescription or, possibly, even a doctor’s visit. While bacteria can become immune to one type of phage, it’s far easier to develop new phage than it is to develop new classes of antibiotics. Phage are literally everywhere, and phage ‘development’ is often just a matter of finding the right spoonful of sewage, then carefully extracting and culturing those phage which could be useful. Also, the phage themselves can adapt within hours to overcome host resistance.

The USDA has done some significant research on phages and their commercial application and seems generally receptive to their use, however it’s impossible to patent most phage since they’re naturally occurring and commercial adoption seems slow going. Attempts by companies like Intralytics to develop patentable injectable phage for treating bacteria in the bloodstream seemed to have failed for the time being (though they did come out with a phage based anti-listeria spray in 2006.) FDA approval, in particular, is expensive. And even though developing new phage is a cakewalk compared to developing a new class of antibiotics, a company cannot prevent others from stealing and reproducing their product.

The Eliava institute and the USDA are good starting points for those interested in the topic. The silence on this area of research is near deafening, considering the potential upsides. Eliava was looking at opening clinics in Mexico or Costa Rica. I don’t know what became of those. There’s some limited work being done in Poland. And there seem to be some folks in China doing work or treatment with phage, though they didn’t consider themselves free to talk to me about it, for a variety of possible reasons. The wikipedia article on the topic is pretty good for general background.

One of the things about phage is that they tend to be very specific. So you can have a phage that will take out a pathogenic strain of E. Coli while leaving a benign strain alone. The good side of this is that you have much fewer of the side effects that you mention, like losing all your gut flora (though you can still theoretically run the risk of shock due to a massive, sudden bacterial die-off, the same as you would with antibiotics.)

The bad side is that… well, phage are very specific. You need to either know exactly what you’re shooting for, which is labor intensive and time consuming, or else you can use a few hundred different phage at once for in what’s popularly referred to as a ‘phage cocktail.’ And even then, it’s a lot easier to miss your target when you’re using phage. The Eliava institute has tried marketing a product called pyophage, a bandage impregnated with numerous different phage, for a bandage designed to kill some of the worst bacterial nasties. At the very worst, the bandage is just an ordinary bandage.

Also, you have to make sure that your phage is exclusively “lytic”. That means your phage needs to be the type that bursts out of and kills its bacterial host cell, rather than hiding inside it and occasionally reproducing. It isn’t difficult to make sure that your phage is lytic, however.

A sampling of relevant articles;

USDA article

We now present data showing that efficient phage therapy of staphylococcal infections is no longer a treatment of last resort (when all antibiotics fail), but allows for significant savings in the costs of healthcare.

link

The mutability of bacteriophages offers a particular advantage in the treatment of bacterial infections not afforded by other antimicrobial therapies. When phage-resistant bacteria emerge, mutation may generate phage capable of exploiting and thus limiting population expansion among these emergent types. However, while mutation potentially generates beneficial variants, it also contributes to a genetic load of deleterious mutations.

link (translation; while a disease can evolve to be resistant to phage, phage can, itself, evolve to overcome resistance. But since evolution requires mutations, if phage has too many mutations it won’t be strong enough to work.)

The bactericidal activity of bacteriophages has been used to treat human infections for years as an alternative or a complement to antibiotic therapy. Nowadays, endolysins (phage-encoded enzymes that break down bacterial peptidoglycan at the terminal stage of the phage reproduction cycle) have been used successfully to control antibiotic-resistant pathogenic bacteria in animal models. Their cell wall binding domains target the enzymes to their substrate, and their corresponding catalytic domains are able to cleave bonds in the peptidoglycan network. Recent research has not only revealed the surprising rich structural catalytic diversity of these murein hydrolases but has also yielded insights into their modular organization, their three-dimensional structures, and their mechanism of recognition of bacterial cell wall. These results allow endolysins to be considered as effective antimicrobials with potentially important applications in medicine and biotechnology.

link

Preclinical testing of the experimental pseudomonas phage preparation on white mice revealed that the therapeutic efficacy of the phage preparation was higher (80-100%) than that of the antibiotic-ciprinol (50-80%). Noteworthy, 100% therapeutic efficacy was observed after combined application of the antibiotic and the phage preparation.

from the Eliava Institute

Isolation and characterization of nine bacteriophages that lyse O149 enterotoxigenic Escherichia coli.

Another route to countering antibiotic resistant bacteria is to attack the antibiotic resistance itself.

[Scientists] have found drugs called bisphosphonates block an enzyme used by bacteria to swap genes, and acquire or spread resistance to antibiotic drugs.

They also showed that interfering with the enzyme could destroy drug resistant bacteria cultured in the lab.

..

Exactly how bisphosphonates destroy each bacterium is still unknown, but the drugs were potent, wiping out any E. coli carrying relaxase.

He stressed the latest study was at a very early stage, and that bisphosphonates had only been shown to have an effect against one type of bacterium – E. coli.

link

pubmed cite 2007 Jul 24

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Posted in My Blog on 06/10/2008 01:38 pm
 

2 Comments

  1. Bill Riedel

    Congratulations – this is a great article.

    I personally think that Thomas Haeusler’s book – “Viruses vs. Superbugs – a solution to the antibiotics crisis?” and his website http://www.bacteriophagetherapy.info are the best starting points for people wanting information on phage therapy. I found the book in big book stores as a shelf item and believe it is out as a paperback. There is also a Canadian film entitled: Killer Cure – The Amazing Adventures of Bacteriophage – it shows patients being treated in the Georgia clinic in Europe.

    Reply

  2. Thanks for the info, Bill! I’ll have to check out the link.

    Reply

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