I Need Help With Phage Therapy

[XrenegadeZ]

I understand the whole concept about replacing antibiotics with bacteriophage because of the increase in antibiotic resistant bacteria, but what i dont understand is how bacteriophage can be of better use in tackling bacteria resistance.

 

First of all bacteriophage infects bacteria with its viral DNA and then makes multiple copies of the virus using the bacteria's cell replication machinery. Now my first question is this, how can a virus which infects bacteria and makes multiple copies of the infected bacteria, be more effective than antibiotics which destroys bacteria without making any copies of it?

 

How can the effectiveness of bacteriophages against bacteria be tested against the effectiveness of antibiotics in a lab experiment? Answers would be greatly appreciated... Hugo

[Psycho]

It doesn't make multiple copies of the bacteria it makes multiple copies of itself, the bacteriophage. When the bacteria lysis releasing the phages they can infect other bacteria until they are eradicated therefore meaning there is no more bacterial infection.

 

The problem with the whole idea is that some bacteriophages have been linked with increased mutation rates in ordinary body cells and therefore an increase in the prevalence in cancer rates, however it depends on the type of phage used.

[XrenegadeZ]

It makes more sense now... i guess it means i didnt understand the whole concept properly. Thanks for clearing it up and a huge bonus for mentioning the disadvantages of using it to destroy bacteria,

[Wolfkeeper]

Ummmm. Phage don't cause increase in cancer rates in any way. They don't infect humans at all.

 

They can however change the behaviour of bacteria, and this can make them more pathogenic (or less pathogenic for that matter). Cholera for example can occur when a Cholera phage infects a particular, otherwise harmless bacteria.

 

But this isn't such a problem for phage therapy- the phages chosen are ones that kill the bacteria and do not trigger pathology.

 

The only major worry I'm aware of is that phages could theoretically transfer antibiotic resistance from one bacteria to another; but it's never been seen in real life, and because the phages kill bacteria so well, it's very unlikely to be ever seen.

[hitmankratos]

This is very interesting...

So it is possible that in a few years people won't use certain antibacterias anymore because of that resistance?

How could that be showed in a lab experiment?

 

And how can we check that they are effective in a lab anyway?

 

Thanks in advance.

[Psycho]

This is very interesting...

So it is possible that in a few years people won't use certain antibacterias anymore because of that resistance?

How could that be showed in a lab experiment?

 

And how can we check that they are effective in a lab anyway?

 

Thanks in advance.

If you put the phage on a plate on a bacterial lawn and the bacteria lysis forming plaques you know it has worked.

 

Antibiotics will always be used as in most cases the most common strain of the bacteria isn't resistant plus they are far cheaper than any phage therapy, however they would be more useful in cases when the bacteria have become resistant and antibiotics are of little use.

 

Another use for them could be if someone is allergic to the antibiotic required however they would have to be allergic too several before it would become a desired option.

[Dnasis]

The only dissadvantage of Phage therapy is the immune system recognising it as foreign and thus can only be really used once. Phages are also temperature sensitive and their use for antibacterial therapy is a long way off. Also the half life of Phages is also limited and thus have to be kept in continual growth which in itself is a problem due to the purification process can damage these sensitive little critters

[CharonY]

Actually there are quite a number of disadvantages:

 

1) specificity. Phages often have a very narrow host range, so one hast to be very sure which bacteria are to be targeted. Even so there is some chance that the specific strain might be resistant.

 

2) it is not always easy to maintain the phages in a lytic cycle.

 

3) as already mentioned, the risk of phage induced horizontal gene transfer. With some bad luck you may transfer pathogenicity genese to otherwise harmless bacteria, thus worsen your condition

 

4) getting purified phage preparations that are free from bacteria is not that trivial or cheap

 

5) dosages are hard to maintain due to the replicative nature of the virus

 

That are just a few that I can think of right now. I am sure there is more.

[hitmankratos]

3) as already mentioned, the risk of phage induced horizontal gene transfer. With some bad luck you may transfer pathogenicity genese to otherwise harmless bacteria, thus worsen your condition

 

5) dosages are hard to maintain due to the replicative nature of the virus

 

For these 2, you just have to use the right phage to attack the right bacteria...If it's a specialist who does that, then there shouldn't be anyproblem, no?

 

And new antibiotics are more expensive to develop then any phage...

 

So I think they're pretty much equal...

 

The only big problem I've heard of would be the immune system blocking the phage...

[CharonY]

Nope, the transfers occur because the phages do not always package in the right DNA. As such you cannot easily control whether the bacteria you are targeting might not get something that makes them more virulent. Also, viruses can mutate very easily.

Regardless, as they replicate you cannot control the dosage, regardless with which specificity. Phage production is also pretty tricky, make no mistake.

[Phil]

Hello,

I have a question for those of you working with phages. I have isolated some temperate phages by mitomycin C induction of lysogenic bacterial strains. Now I need to amplify these phages and thus I need to find indicator strains for which the phages will be lytic and won't integrate in the bacterial genome. Accordingly, I was wondering if somebody knows why temperate phages can follow the lysogenic cycle in some bacterial strains while the same phages will be lytic and won't integrate the bacterial genome in other bacterial strains ?

 

Thank you!

[CharonY]

Generally speaking phages "determine" whether they become lysogenic or lytic via a switch, usually a (or several) regulatory proteins. Best known systems involve a repressor. Now the interesting part is that many phages couple their regulation with regulation of the cell, often stress-relevant cell answers. For instance, the lambda repressor usually keeps the phage lambda in a lysogenic stage.

 

Once you stress the cell it may start a so-called SOS-answer, which activates the stress-related protein RecA which then cleaves the repressor of the phage, thus starting the lysogenic cycle. This coupling allows to phage to react to stresses of the cell and abandon it, if things go bad, so to say. Similar mechanisms exist for most phages around. Strains in which the lysogenic cycle is abolished likely have some kind of mechanism that interfere with the phage regulation, thus preventing entering lysogenic cycle (though the reverse also happens).

[Ulna]

I have a question.

Say someone has bacterial leprosy (Not tuberculoid) with lesions etc a proper infestation and phage therapy is used. Well lots of bacteria will surely increase the phage population and the bacterial population starts to decrease, is there a chance that phage may mutate to infect human tissues, due to the decreasing numbers of bacteria they can infect?

[CharonY]

It is somewhat unlikely. The structures of pro- and eukaryotic cells (as well as transcription machinery) are so different that different mechanisms are required for viral infection and replication in each respective host.

It is possible to artificially introduce phage material into eukaryotic hosts, though.

[Ulna]

You're right, i didn't think of the difference between prokaryotic and eukaryotic cells - oops.