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Anatomy of a Virus
Roland Piquepaille writes "No, I'm not talking about a computer virus here, but about a real one, the Epsilon 15, which attacks the bacterium Salmonella. By writing a few lines of computer code, biologists from Purdue University have found a way to control a high-resolution microscope. This allowed them to look inside a virus. While previous teams were able to visualize the highly symmetric outer shell of other viruses, these researchers were able to see the whole structure of Epsilon 15, including its tail, its genome and even its core. This better knowledge of viruses which attack bacteria could lead to great advances in medicine, especially when antibiotics become inefficient because of bacteria resisting them."
Granted, they made an improvement on existing methods used to interpret cryo-EM data, but "looking inside a virus" has definitely been done before, and for more important viruses.
Already being tried. AFAIK the Russians had a go at using bacteriophage therapy but nothing much came of it. People have tried and failed at using phage's (viruses that infect bacteria) to try and treat bacterial infection. Might have some use but I doubt it. The host immune system tends to get in the way.
y if you're interested
See http://en.wikipedia.org/wiki/Bacteriophage_therap
As far as I know, the use of bacteriophages to fight bacterias has been mainstream for years in Russia. A recent article in Science et Vie explained this method and why it was possible to use it : there are so many different bacteriophages that they might outnumber the number of existing bacterias (a good thing, because that implies therefore a kind of competition between viruses, which means the most efficient will emerge in the long run :-) )
The article also explained that what wad actively sought was a bacteriophage attacking Koch bacillas, because some strains are now resistant to the two antibiotics used against them (named here P.A.S. and Rimifon). Once we have located the right bacteriophages killing them, we shall be able to forget antibiotics (viruses, however, might have their own side effects too... Wait and see)
Could be some Nobel prize in the air. I hope it will be granted to the people who deserve it, whoever they are, rather than to other teams just using the ideas of others and presenting them as their owns. The "Not invented here" policy has probaby killed enough people like that :-(
Signature omitted in order to save space. Thanks for your understanding.
There are some movies of this work in the supplementary info for this article. These illustrate the various "bits" of the Epsilon-15 virus.
It all goes to show that there is some really good work going on in three dimensional imaging of very small things. We're even seeing parts on the inside of these small things - it's just spectacular.
.. paranoid crackpot leftover from the days of Amiga.
There was a very interesting TV special about this some seven or eight years ago as well. It had interviews with Georgian specialists in Tbilisi and an extensive history, plus their methodology. Further information here and here.
Rather than having inherent problems with the host's immune system, it seems to have fallen afoul of the Not Invented Here syndrome.
Happily, it looks like this medical technology is coming back out of necessity.
In times of trouble, the smell of frying onions usually gives confidence and comfort.
Also I'm sure they had a very good reason for picking this virus as a first from a virologist point of view, whereas people suggesting they should have picked something 'more important' like AIDS are probably saying that because that's the only virus they know (if they even know the difference between a virus and bacteria - not to mention phage...)
Again a bit of insight, combined with reading TFA in question and perhaps a quick visit to Wikipedia would create much more useful reply comments... (and don't give me any of that "you must be new here" crap...)
www.tribalnetworks.org - helping tribal people around the world to own their own means of high-tech communications
Before anyone begins, the link goes straight to the article, not Roland's blog.
Keep up the good work ScuttleMonkey.
May the Maths Be with you!
The Soviet work on bacteriophage therapies probably was ignored for Not Invented Here reasons. But it's been looked at pretty thoroughly in the last few years and doesn't appear to have any great value.
What I'm listening to now on Pandora...
Not really a debate, it depends on your point of view. What sets virii apart from bacteria is that virii can't reproduce by themselves (they abuse other organisms for that). Drop a bunch of virii in an otherwise sterile environment, and nothing much will happen. Drop some bacteria in an otherwise sterile (but suitable) environment, and they'll quickly reproduce. But hey, this is kids biology stuff...
What it looks like under a microscope doesn't change any of this.If my hazy memory of high school biology holds true, that "rocketship" virus is the T7 phage that attacks tabacco.
Please read articles before citing them. This reference is about bacteria given to mice that were PRETREATED with phage. This was not a challenge study. This only points to the fact that this therapy has some potential. Preventing bacterial growth occured in vitro - ie on a petri dish.
I agree that it probably isnt in the interests of big biotech to market such novel treatments as it takes a chunk out of their antibiotic sales. However, if it did work, I bet you some smaller biotech startup would have sprung up by now - hangon they have!
Also manufacturing treatments involving live virus is difficult to say the least.
Around 2000, this was the wonder cure for bacterial diseases. General public didnt hear about it as stuff like this never hits the general news unless people die or the press decide to hype it up.
Phages, by definition, are anti-bacterial viruses! Many bacteria have such enemies -- part of the circle of life don't ya know. Anyway, "scientists" don't need to create their own-- they just need to learn about the phages that are out there now and manage them as needed. This is an old concept known as biological control.
No, "doesn't appear to have any great value" as in "doesn't appear to work".
What I'm listening to now on Pandora...
How long before scientists are going to try and create their own anti-bacterial virus, a la some Michael Crichton novel?
Depends on who you ask. Some people would say we've done it already.
A NYC lawyer blogs. http://www.chuangblog.com/
"Phage" is Greek for "eater". "Bacteriophage" is a virus that attacks bacteria.
Viruses are almost always entirely species specific, mostly because they rely upon the structure of the cells they attack. The structures can include any of the cellular membrane or cell wall, the various DNA transcriptase and polymerase enzymes and the nuclear or chromosomal DNA itself. Bacteria are simple eukaryotic organisms so lack a number of other structures that can be abused by viruses and virus-like agents, and consequently bacteriophages are relatively simple DNA viruses.
Bacteriophages are extremely common, particularly in bacteria-rich open water, especially in plankton-rich parts of the oceans, where there can be much more than 1E10 viruses per litre.
A typical human being will encounter billions of viruses a day, almost none of which will challenge the active immune system -- most will be blocked by the passive systems (the skin, the mucus membranes...).
Bacteriophage therapy bypasses the passive membranes entirely via direct application to an infected wound or by intravenous injection. Since the applied or carefully injected viruses are monoculture and highly species-specific, they do not challenge the body's primary immune response mechanisms except to the extent that any foreign protein in the blood would in dilute amounts.
The important consideration is that the rapidly-responding innate immune system is unlikely to challenge an injected bacteriophage. The viruses cannot infect the host cells and consequently do not distress tissues (danger model and simple phagocyte chemotaxis) and are unlikely to be associated with TLRs in the innate immune system, or even encounter NODs (PAMP/PRR model).
The adaptive immune system is much slower, which is why people are ill for several days when infected with a new pathogen. It essentially exists to memorize successful attacks against serious infectious diseases the host survives, so as to mitigate or prevent future infections by the same (or very similar) microbe.
The plausible risks to the therapeutic bacteriophage itself when introduced into a human being with a normal immune system are mainly that the human's fever and swelling responses triggered by the bacterial infection physically keep the viruses from infecting their target bacteria, or that the human had tissue insulted by a highly similar virus (improperly injected such that it remained at high concentration, perhaps) at some time in the past.
However, the amount of virus to be injected is tunable, and it is much more likely that in the short term the bacteriophages will find, attack and kill most of its target bacteria than they will be wiped out by the patient's immune system.
The major practical problems with bacteriophage therapy is that they are like very narrow-spectrum antibiotics. You need to culture the bacteria in vitro and check its susceptibility to specific virus strains, which can take a full day or more. Moreover, if there are multiple strains of infective bacteria, you can "miss" with the culturing and only partially treat the patient. The time and possibility of "misses" going undetected for a while account for the popularity of wide-spectrum antibiotics.
Unfortunately, wide-spectrum antibiotics are an evolutionary selection pressure on microbes succeptible to them... those that aren't killed because of some inheritable trait are likely to pass that trait onto their offspring. Staph. aureus, a common skin-infection bacterium, is particularly good at this, and there are strains which are resistant to very strong wide-spectrum antibiotics and even some semi-wide-spectrum ones targetting gram-positive bacteria like methicillin and vancomycin -- these are the frightening MRSA and VRSA "superbugs".
The scary thing is that Staph. aureus bacteria are often not the bacteria being treated with wide-spectrum antibiotics like penicillin, so they are overlooked. Survivors may pass on resistance.
Very narrow-spectr
"The US way" (never mind that the pattern is just as likely to be used by large Swiss or Danish pharma companies as American ones) will run into the problem that there is a lot of similar work covered by patents in countries which have recently become full members of WIPO (and the European Union too) and thus by treaty have prior claim to patent protection in the USA.
However, actually engineering a better delivery mechanism or greater effectiveness could be extremely useful, whether it is promoted by or simply allowed by "the US way".
Your "clusterbomb" suggestion has two problems in that if the phage therapy is used to attack and an E. coli strain in the gut and get it to produce a bunch of antibiotic prior to being lyse, there is a risk that the antibiotic will kill the attacked bacteria before it explodes and releases copies of the bacteriophage (so, the antibiotic merely reduces the effectiveness of the virus and nothing else), or it will introduce tiny amounts of wide-spectrum antibiotic to succeptible microbes also in the gut (so, the antibiotic serves as a tiny selection pressure in favour of resistant genotypes).
Maybe a neater idea would be to manipulate the viral DNA to have it code a mutagen that affects the viral DNA itself in a way that encourages parallel evolution with surviving target bacteria, and another "edit" which makes the virus itself more susceptible to ex vivo conditions to limit its spread in the wild. (The latter seems like a very Monsanto thing to do...)
No conventional microscope is involved: A transmission electron microscope is used for this kind of work, with samples that are rapidly cooled to liquid nitrogen temperature to vitrify them. Then complex 3D image reconstruction techniques are used on the images to generate the result.
Typically this involves finding the images of the viruses in the field of view, alignment and centering, similarity clustering of the (grainy) images, averaging of the clusters, determining their relative orientation, 3D reconstruction, and back-projection to compare the result with the input images. Symmetry helps a lot.