![[personal profile]](https://www.dreamwidth.org/img/silk/identity/user.png){kind=small}
Gut Science!
So this week I was debating going to seminar, because the email said it was about salmonella and metals and I am not terribly interested in infections bacteria-based disease. But then I went because I had to be on that side of campus anyway, and I am so glad I did.
The story was thus: when you get any kind of food poisoning/virulent gut-invaders, your body goes through an inflammatory response. That is, cells in the gut go, "There is something here that should not be here! Alert! Summon the immune cells!" This is followed by the immune cells going, "On alert! Swell up to fill the intracellular gaps and prevent anything getting in to the blood! Release the cytokines!" And it does work, in the sense that invaders do not get in to the blood, which would indeed be very Bad. The odd thing was that, as far as we can tell, doing this also allows the invader to successfully outcompete the symbiotic bacteria in your gut, essentially killing and eating them and within a few days becoming more than half the total bacteria.
And this researcher went, "Huh. That's weird. Why would we use a response that helps the invaders?"
So she went and looked into each step of the inflammatory response. A bunch worked inasmuch as the salmonella, which she is using as a model Deadly Invader, could not grow in the gut. Unfortunately, shutting those down also meant that they could get into the blood, so not very helpful. But she followed up on those, and eventually through the use of genetically modified mice, figured it out.
What happens is that the cytokines, which are a chemical signal, tell the gut cells to release small bacteria-killing proteins. This is entirely logical, if you are trying to kill the invader. But the way they work is by finding special chemicals that bacteria make to go grab iron and magnesium and zinc, and locking them up; this starves the bacteria cells of vital metals, and thus they die. Deadly Invaders, however, have caught on to this trick, and evolved to make chemicals that are just different enough that the proteins cannot recognize them, although they still grab and deliver metals.
As a result, making these proteins successfully starves your friendly not-painful symbiotic bacteria while doing absolutely nothing to the invader. Thus, the invaders take over.
Aha, you say. Simply stop making these proteins. In fact, mice which simply don't have the genes for these proteins appear to be more salmonella-resistant for just that reason. But a number of harmful bacteria that have not been in the disease-causing business as long as salmonella do get starved and killed off by this mechanism, so just shutting it down is not a good idea.
The solution is, in fact, kind of counter-intuitive. Instead of trying extra hard to kill invaders, we add competitors. That is, we find a bacteria that makes modified metal-grabbing chemicals, just like the invaders, but which are happy to live in us as symbiotes. Actually they make even more different kinds of metal-grabbers, which means they get more metals sooner, and can grow faster, and totally outcompete the invaders - all while being human-friendly.
This is a probiotic treatment, using a (totally friendly!) strain called E. coli Nissle. Nissle has been used as a human treatment against diarrhea since WWI, so we know it is okay. And in mice at least, just one treatment two days after giving them the salmonella-laced food cuts salmonella growth by 1000 for at least three weeks. (That is as long as they did the study.) I, as a sufferer of Crohn's, which causes chronic inflammation and thus periodically starves my symbiotes dead, would love some gut-bacteria that could survive my body's hostile envoironment. I am sure others with IBD or colitis would like the same.
The only real issue? Nissle is illegal in the US, because it is a strain of E. coli, and must, according to politicians, be DEADLY. (For reference, 2-3% of the bacteria naturally found in your gut are also types of E. coli.) Stupid non-sciencey people making laws about the applicability of life-saving Science!
The story was thus: when you get any kind of food poisoning/virulent gut-invaders, your body goes through an inflammatory response. That is, cells in the gut go, "There is something here that should not be here! Alert! Summon the immune cells!" This is followed by the immune cells going, "On alert! Swell up to fill the intracellular gaps and prevent anything getting in to the blood! Release the cytokines!" And it does work, in the sense that invaders do not get in to the blood, which would indeed be very Bad. The odd thing was that, as far as we can tell, doing this also allows the invader to successfully outcompete the symbiotic bacteria in your gut, essentially killing and eating them and within a few days becoming more than half the total bacteria.
And this researcher went, "Huh. That's weird. Why would we use a response that helps the invaders?"
So she went and looked into each step of the inflammatory response. A bunch worked inasmuch as the salmonella, which she is using as a model Deadly Invader, could not grow in the gut. Unfortunately, shutting those down also meant that they could get into the blood, so not very helpful. But she followed up on those, and eventually through the use of genetically modified mice, figured it out.
What happens is that the cytokines, which are a chemical signal, tell the gut cells to release small bacteria-killing proteins. This is entirely logical, if you are trying to kill the invader. But the way they work is by finding special chemicals that bacteria make to go grab iron and magnesium and zinc, and locking them up; this starves the bacteria cells of vital metals, and thus they die. Deadly Invaders, however, have caught on to this trick, and evolved to make chemicals that are just different enough that the proteins cannot recognize them, although they still grab and deliver metals.
As a result, making these proteins successfully starves your friendly not-painful symbiotic bacteria while doing absolutely nothing to the invader. Thus, the invaders take over.
Aha, you say. Simply stop making these proteins. In fact, mice which simply don't have the genes for these proteins appear to be more salmonella-resistant for just that reason. But a number of harmful bacteria that have not been in the disease-causing business as long as salmonella do get starved and killed off by this mechanism, so just shutting it down is not a good idea.
The solution is, in fact, kind of counter-intuitive. Instead of trying extra hard to kill invaders, we add competitors. That is, we find a bacteria that makes modified metal-grabbing chemicals, just like the invaders, but which are happy to live in us as symbiotes. Actually they make even more different kinds of metal-grabbers, which means they get more metals sooner, and can grow faster, and totally outcompete the invaders - all while being human-friendly.
This is a probiotic treatment, using a (totally friendly!) strain called E. coli Nissle. Nissle has been used as a human treatment against diarrhea since WWI, so we know it is okay. And in mice at least, just one treatment two days after giving them the salmonella-laced food cuts salmonella growth by 1000 for at least three weeks. (That is as long as they did the study.) I, as a sufferer of Crohn's, which causes chronic inflammation and thus periodically starves my symbiotes dead, would love some gut-bacteria that could survive my body's hostile envoironment. I am sure others with IBD or colitis would like the same.
The only real issue? Nissle is illegal in the US, because it is a strain of E. coli, and must, according to politicians, be DEADLY. (For reference, 2-3% of the bacteria naturally found in your gut are also types of E. coli.) Stupid non-sciencey people making laws about the applicability of life-saving Science!
no subject