Bacteriophage therapy

[joesixpack]

Something I just stumbled across. Is it actually a treatment that holds a lot of promise or is it pseudoscience? What I've read of it sounds interesting, but I'm no microbiologist, and the fact that research has been largely confined to Georgia and the former USSR makes me automatically suspicious. Yes, I know that the USSR had top shelf scientists, but they also had Lysenko and other top shelf charlatans.

Oh, and there's a Liz Taylor connection, too.

[The Don]

Dunno, but I saw a TV programme on the BBC about 20 years ago just after the fall of communism saying how it would revolutionise the treatment of Antibiotic-resistant bacteria.

[BowlOfRed]

The ideas are legitimate. But when "universal" antibiotics were the rage, there was very little research done in the west when phages have very specific impacts. I've heard several updates from teams in the popular press that have been working on phage therapy in recent years.

[Tracy Dalziel]

Its far from new, and never completely lost popularity in parts of the former eastern block and historically even in the west some big pharma players (if I remember correctly, Lilly was one) marketed phages. They were largely overshadowed by antibiotics because these tended to be more convenient, even the narrow spectrum ones generally targetting at least a fair handful of pathogenic genera compared with phages which have a very limited host range. It is effective and there were news reports recently of the successful use of phages to treat burns in soldiers that were infected with pan resistant bacterial strains. Interest in the field is gaining ground again.

[BenBurch]

Phages suffer from an effect related to their effectiveness; If you are very sick, phages kill the pathogens so quickly that the results are toxic.

[Tracy Dalziel]

Phages suffer from an effect related to their effectiveness; If you are very sick, phages kill the pathogens so quickly that the results are toxic.

But do phages pose a greater disadvantage in this regard ? This can happen with conventional therapy as well. For example, treatment of pneumococcal meningitis generally requires a bactericidal agent but most of these (eg penicillins) have a lytic mechanism of action which causes large bursts of pneumolysin to be released, increasing the risk of neurologic damage, its often catch 22. Ditto with Gram-negative sepsis and endotoxic shock or the Herx reactions which are a hazard in treatment of spirochaetal diseases.

[BenBurch]

Not information I have. Sorry.

[joesixpack]

Thanks everyone for the replies. The tone of the articles I'd seen on this were a bit "Mainstream Science and Big Pharma don't research this". That was tripping my BS meter.

I've found a bit more information and it's really quite interesting stuff.

[Toke]

Last I heard they were also a part of the immune system.

Todays news have an article (http://politiken.dk/videnskab/ECE1474455/danskere-finder-middel-mod-uhelbredelige-sygdomme/) on some way to make multiresistant bacteria vulnerable to antibiotics again, perhaps bacteriophagers will remain a niche?

[joesixpack]

Bumping this because I have another question about phages. I was talking about Bacteriophage therapy with my son and he asked one of those very simple but unanswerable questions that kids have a knack for asking. "Why don't bacteriophages eat normal cells?"

The best guess he and I could come up with was that the phages could only feed on prokaryotes because their DNA isn't inside a nucleus. Does anyone here know? I'm suddenly desperately curious.

[cosmicaug]

Bumping this because I have another question about phages. I was talking about Bacteriophage therapy with my son and he asked one of those very simple but unanswerable questions that kids have a knack for asking. "Why don't bacteriophages eat normal cells?"

The best guess he and I could come up with was that the phages could only feed on prokaryotes because their DNA isn't inside a nucleus. Does anyone here know? I'm suddenly desperately curious.
It's more than that. There are a number of things necessary for a viral infection to be successful.

For instance, in something like the T7 bacteriophage, you appear to be on the right track in your speculation in that T7 RNA polymerase will locate cytoplasmically which kind of breaks the trascription-translation sequence --as well as T7 genes will lack the appropriate polyadenylation sequence used in eukaryotic translation (I welcome anyone with more intimate knowledge of the T7 bacteriophage to correct me if I am mistaken). I am pretty sure it is likely that you would find a bunch of such non-negotiable obstacles to eukaryotic cell infection for most, if not all, bacteriophages.

However, even if that were not the case, in bacteriophages (and any other virus, really) the first step required for infection is going to be an attachment phase which will be mediated by binding to a "receptor". Assuming that by "normal cells" you mean the human cells of a patient, the correct receptor will not be there so the viral infection process will never even get to start (regardless of whether the animal cell would be compatible with any other phases of the infection process).

So, basically, bacteriophages would not even be able to get into the eukaryotic cell.

[Lukraak_Sisser]

Bumping this because I have another question about phages. I was talking about Bacteriophage therapy with my son and he asked one of those very simple but unanswerable questions that kids have a knack for asking. "Why don't bacteriophages eat normal cells?"

The best guess he and I could come up with was that the phages could only feed on prokaryotes because their DNA isn't inside a nucleus. Does anyone here know? I'm suddenly desperately curious.

A bacteriophage is like any other virus. It recognizes and infects a very specific range of cells. Once infected they integrate into the DNA and abuse the cell's internal systems to make more phages.
Infection occurs by recognizing specific external proteins where even minor differences can stop infection. Given the huge difference between human cells and bacteria even IF a bacteriophage somehow entered a human cell it's genetic code would be incompatible with the internal workings of the cell.

[Soapy Sam]

From the evolutionary POV, a phage that attacks the wrong type of cell is likely to vanish from the gene pool. Maybe once in a million times of course, one will get lucky and find itself in a different type of cell, where it can thrive. At that point we might see a phage "speciation event" and perhaps a new disease.

[Modified]

Cancer-killing virus treatments will soon be on the market (already are in China, I believe). I expect some day we'll have engineered viruses that attack only subcutaneous fat cells.

[joesixpack]

Cancer-killing virus treatments will soon be on the market (already are in China, I believe). I expect some day we'll have engineered viruses that attack only subcutaneous fat cells.

Oh what a boat load of bacon I'll be eating then! And wash it down with some beer!

[BenBurch]

Now, if you look at a virus as an organic nanomachine, I think you can see some of the promise of nanotech realized through clever virus design.

[cosmicaug]

Cancer-killing virus treatments will soon be on the market (already are in China, I believe). I expect some day we'll have engineered viruses that attack only subcutaneous fat cells.Oh what a boat load of bacon I'll be eating then! And wash it down with some beer!

There's a paper out there from a few years ago where they created a fusion protein combining what is essentially a death signal (I'm assuming some kind of apoptotic trigger) with an adipose tissue receptor ligand sequence (I don't recall the receptor but it's of the sort which gets internalized after binding). It killed fat cells with specificity.

Anyway, I'm not so sure you want to go too crazy with the bacon if you don't have a sink for the triglycerides.

[joesixpack]

Anyway, I'm not so sure you want to go too crazy with the bacon if you don't have a sink for the triglycerides.

I'll just assume they'll come up with a virus to take care of that (and fix my liver while they're at it) as well. Moderation be damned.