Lysin is an enzyme used by bacteriophages to break out of bacteria they’ve infected and reproduced within. Viruses for each kind of bacteria have a unique kind of lysin. There was a recent report about the use of lysin to kill anthrax here.
My questions:
This looks like lysins could revolutionize the treatment of bacterial infections. What kind of timeline are we looking at for lysins to be the principal method of treating them?
How likely is it that bateria will develop resistance to lysins as they have to antibiotics?
Would it be possible to develop a drug that interferes with the lysin of viruses and prevent their function? This might be effective in fighting viral diseases such as AIDS.
For the first time in a decade I don’t have easy access to Nature. So I can’t read up on the details of the lysin’s activity, but I’ll take a whack at your questions.
Its hard to say. I think a lot more needs to be done to determine how effective they are on various pathogenic bacteria.
Granted “it would take the bacteria more than a while to figure out how to fundamentally restructure their cell wall”, but it’s certainly not ridiculous to assume they can’t. When you reproduce in the ball park of five times an hour, natural selection occurs rather quickly. Traditional antibiotics have targets that are essential to the function and/or replication of the cell, yet bacteria develop a wide range of clever workarounds to survive and multiply. It may be tougher, but I doubt resistance is impossible.
Viruses that infect human cells don’t have lysins, AFAIK. In fact many bacteria would prefer not to kill the host cell at all. Some viruses, like herpes simplex, go a long way to protecting the infected cell from immune system attacks. Other viruses, like HIV, will actually insert its DNA into the DNA of the host cell, so killing the cell is counterproductive. And while some viruses will replicate themselves then burst out of the cell, they probably do not use lysin-like enzymes.
See, you bring up viruses and I shift back to grad student doublespeak mode. Sorry about that.
Essentially, I’m saying that in my opinion, it is quite possible that bacteria will develop resistance to lysins. But again, not knowing the details of the research performed by a lab in the top biomedical insitution in the nation, I’m hesistant to say anything with complete authority.
“Lysin is an enzyme used by bacteriophages to break out of bacteria they’ve infected and reproduced within. Viruses for each kind of bacteria have a unique kind of lysin. There was a recent report about the use of lysin to kill anthrax here.”
Bacteriophages are viruses than enter bacteria, reproduce, and then cause the production of a lysin which pops the bacterium wide open, killing it. I predict that the lysins will revolutionize the treatment of bacterial infections to the same extent that bacteriophages have, following the same timeline (bacteriophages were first described in 1917).
Why exactly doesn’t phage therapy work? Somewhere I read that the human immune system is too good at removing them from the body. But antibiotics are removed from the body fairly efficiently and we get around that by reintroducing it every so often (sometimes several times a day). Will this not work with phages or is there some other problem with them?
I thought all virii worked by inserting their DNA into the cell and forcing the cell to produce more viruses eventually killing the host cell in the process. What makes HIV so nasty is that the cells it kills are our white blood cells that help us fight infection.
IANAD but I would imagine that viral therapy would be difficult because our body would respond to it like any other virus and probably kill it eventually. So the trick would be making a virus that your body does not generate an immune response to, that only targets cells you want killed. Sounds easy enough but there are thousands if not millions of different types of cells that do belong in your body and you have to make sure you make a virus that won’t kill anything you need while it kills what you want it to more effectively and or more cheaply than present day antibiotics.
This thread explains bacteriophages and also includes a link that shows them in action.
The difference with Lysine therapy and phage therapy is in lysine therapy lysine alone is given. The lysine is isolated and dosed, not the virus itself. Viral therapy tend to be ineffectual because we have yet to find a way to get them efficiently to the target organism. The body seems to shed them before they find their target. However with the lysine you can heavily dose and hopefully get higher efficacy.
Bacteria shouldn’t develop resistance to lysine as it doesn’t seem to be genetically targeted therapy. In other words, it seems to work more like rubbing alcohol then penicillin which targets enzymes needed for the synthesis of the peptidoglycan wall. This targeted action of antibiotics allows bacteria to defeat it’s action by mutation.
One of the problems with lysine therapy is it’s lack of efficacy on gram negative organisms. With bacteriophages the viruses have defeated the problem of the cellular membrane with adhesion. So they insert their DNA/RNA through the cellular membrane, and the cellular wall into the bacteria. However, the lysine won’t work on the cellular membrane. It only works on the cell wall. Thus it is ineffectual against gram negatives, which happen to be the larger class of pathogenic organisms.
Lysine therapy is going to be several years down the road for general use. There has yet to be any clinical trials, and the research is preliminary, yet promising.
I can’t imagine a way to make anti-lysine therapy work (although this doesn’t mean it won’t happen). One of the problems with this is that would have to find a way to get your therapy into the cell without destroying it, as lysine works from the inside-out. If you have to destroy your cell to make your therapy work, it’s a bit counterproductive.
I have a slight tickle in the back of mine brain about Bacteriophages. Are those the cool looking viruses that look like moon landers that almost everyone has had to make a model of back in HS/JS?
Anyway, there are a large variety of viruses out there and they all replicate in various ways, but a many human viral pathogens don’t rupture the cell at all.
Check out the diagram of a retrovirus life cycle on this page. The details aren’t really important for this discussion but note the “budding” step. This allows replicated virus particles to be released from the cell without having to pop the cell open.
Many viruses utilize this mechanism to reproduce. If you can fool the immune system into believing that the cell is behaving normally (which many viruses do) then you have a very efficient virus factory which can theoretically produce an unlimited number of virus particles.