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roundtable: the evolving enemy Watch Show 4:
"The Evolutionary Arms Race"
on PBS
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Select a question:
How concerned should we be about becoming infected with resistant bacteria from foods like chicken, beef, and even aqua-cultured fish that may have been grown on diets treated with antibiotics? Will eating less of these foods, perhaps by switching to "organic" chicken, reduce our risk, and do vegetarians have a reduced risk for this reason?
If the use of antibiotics in a widespread fashion at low doses in agriculture, particularly in the raising of animals, is so common and yet so potentially dangerous from the standpoint of evolution of resistance, why is it still the practice? What are the costs and benefits of this practice?
Several people have submitted questions not about antibiotics, but about all of the liquid soaps that are now for sale in supermarkets that are labeled "antibacterial." Do these work like antibiotics in causing further resistance? If so, how, and if not, how is their action on bacteria different than just plain soap?
Americans now seem to be getting fanatic about sterility, and people are trying to raise their children in an almost "germ-free" environment. We have a question from a woman who says that she has several friends, young mothers, generally, who seem to overuse antibacterial products. She asks: Is it not true that the presence of some "germs" in moderation is actually good for the development of our immune system?
In one of the programs in the Evolution broadcast series, there was the story of the leafcutter ants that culture Streptomyces bacteria on their bodies and seem to use those bacteria to apply antibiotics to keep their fungal farms parasite free. This has been inferred to mean that somehow the Streptomyces and the antibiotics they produce have been evolving with the enemy, and this is a kind of use that appears to have been going on for 15 million years without permanent resistance being developed. Is there anything we can do to put ourselves in that situation versus the more static situation we're in now?
Could you give an explicit description of how evolutionary theory informs integrated pest management? I think the cross-fertilization here between bacteria and antibiotic resistance and agricultural pests and insecticide resistance is very interesting, and I don't think many people make that connection.
Some physicians, who are quite impassioned, say they would like to prescribe fewer antibiotics, but their patients demand them. Since in effect they cannot be absolutely positive there isn't a bacterium involved, when, say, a parent brings in a young child who is ill, and they can't be absolutely certain that there won't be bacterial complications as a result of a viral illness, they would like to know how the public will be educated and who is going to take on the job, so that patients will basically get off the doctors' backs and let their colds run their course.
Another part of that question is that doctors are afraid of being sued if they don't prescribe an antibiotic and a bacterial infection does develop. So from the medical perspective of overuse of antibiotics, how might we address this basic problem in the interface between healthcare providers and the consuming public?
   

 

Q: In one of the programs in the Evolution broadcast series, there was the story of the leafcutter ants that culture Streptomyces bacteria on their bodies and seem to use those bacteria to apply antibiotics to keep their fungal farms parasite free. This has been inferred to mean that somehow the Streptomyces and the antibiotics they produce have been evolving with the enemy, and this is a kind of use that appears to have been going on for 15 million years without permanent resistance being developed. Is there anything we can do to put ourselves in that situation versus the more static situation we're in now?
Panelist Responses: < back to intro page
Stephen Palumbi
The point of that example in the show was that the ants were producing an antibiotic not themselves, but by culturing an organism on their carapaces that would then produce that antibiotic so that the antibiotic could co-evolve with the mold that was growing on the fungus that the ants farmed.
Tamar Barlam
Well, I don't think we need to produce our own antibiotics, but I think that previous discussion actually relates directly to this. Until recently, when we just brought up our children and let them play with other kids and get a bit dirty, there were certain illnesses they got when they were at a certain age as they went through their lives, and now we're interfering with that. There are some interesting studies on kids who go to daycare, who get exposed to childhood illnesses when they're children. They may be a little bit sicker as young kids when they're first going into daycare, but as they get older they have some interesting decreases in other health problems.

I think that we maybe have been in a fairly good homeostasis that we're interfering with by giving too many antibiotics, by overtreating, by using too many antibacterials. So I'm not sure that we haven't, in a sense, been following some of what the ants were doing until we started interfering with it.

If we overtreat, for example, young children, they may not have the appropriate colonization with the organisms that let them produce antibodies that prevent them from getting serious diseases later on. I don't think we produce antibiotics, but we are colonized by bacteria that produce immune responses that do protect us. I think there is a similarity there that we interfere with when we give too many antibiotics, when we use too many antibacterials. We know that when young men join the army and live in barracks, they can be at risk for meningococcal disease, for example. And the ones who are at risk just happen to have been unlucky enough not to have been exposed to the right strains so that they could develop antibodies.

We just increase chances of not having those kinds of protections when we're constantly upsetting our normal bacteria that we're meant, in a sense, to have so that we can prime our immune system.
Stuart Levy
I was fascinated by the leafcutter ant story because of the question that was posed, which is what is the target in the mold that is affected by that hypothetical antibiotic? I don't know whether it has been extracted and discovered, or whether it's one or a number of different antibiotics. What sort of chemical is it, and how does it work? I think that understanding that would be tremendously important to how we deal with the use of antibiotics in human disease.

I will say that, Tamar, if you remember, there are peptide antibiotics that are excreted from the tongue, toads have these things called magainins, there are a lot of little things that are antibacterial that work locally and are in high concentrations that do tend to have antimicrobial activity, and some would pose them as effective in maintaining homeostasis in the presence of some kind of microbiologic harm. I think we're seeing that in a microcosmic way in the ant, but I'd love to see more of what is actually going on, maybe even the helpful fungus is producing something which is adding to this whole stability of that environment, not just the Streptomyces bacteria.
Tamar Barlam
We're not like the ants in the sense that we're producing a specific antibiotic, but if someone went up to those ants and got rid of those bacteria on their back that was making the antibiotic, they would be in big trouble.
Stuart Levy
Tamar, you're absolutely right. I followed your story. For instance, if we had an antibiotic that would destroy the Streptomyces, and then you then added it to the colony, you'd get rid of the bacteria, you'd upset the whole community, and you'd destroy the colony. So I think your point is when we introduce antibiotics into an environment, unless you have a real good reason to target the infectious, life-threatening bacteria, you ought not to use it, because you're upsetting the whole community, only a little bit of which do we understand.
Stephen Palumbi
So the interesting phenomenon is the stability of the interaction between these various players, and one possible explanation for that is that this arms race is proceeding between the mold and the antibiotic-producing bacteria. There are other possibilities as well, and one of them is that the ants in fact do not rely exclusively on antibiotics to control the mold, but they rely on other forms of control as well, particularly manual control -- picking through their fungus and getting rid of the infectious mold.

That is very similar to a strategy that agriculturalists have invented that's called integrated pest management, where you don't rely strictly on chemical control to take care of a pest problem, but you rely on a number of different strategies, including some chemical control. And by relying on a number of different strategies, you effectively slow the evolution of resistance to the chemical, because there are other selective forces that you're bringing to bear on that population. So that's another aspect of the ant system that I think we can learn from, that the integrated pest management is actually a really good idea; it was invented by ants 50 million years ago.
George Beran
This was something I had a broad general knowledge of, but I found it very fascinating the way it was presented, and my thoughts immediately turned from this colony of the ants with their local environment right there inside that underground colony to the environment inside our animals. And I thought, "Oh my word, this is really, really pertinent here."

We are just in the early stages of moving to affect this internal environment in animals in a positive way. And we're calling this strategy the use of probiotics, instead of antibiotics. It also involves the concept of competitive exclusion, in which we are attempting to modify the microbial environment inside the animal in a way that will move away from resistant organisms. And the feeding to animals of organisms that have no resistance to the antimicrobial drug that we're interested in, or that are a source of plasmids which are susceptible to the antibiotics rather than resistant.

At the same time, we are attempting to produce vaccines that will have a defined effect against those plasmids that are resistant. These DNA vaccines hold out some tremendous possibilities for the future, in that they will help us to eliminate that bacterial portion of the animals' inside environment that is resistant to the antibiotics and that we are so concerned about transferring to humans and to other animals. It's an exciting area, and I don't even know where you'd apply at the moment for the research funding for it, but it's beginning to happen.
Stephen Levy
I think evolutionary theory can help enormously, because basically we're talking about an evolutionary event that's driven by an evolutionary process that we understand pretty well, and we know that there are fundamental requirements for evolution to occur. There has to be variation, the variation has to lead to some fitness differential, some change in reproductive ability, and that has to be heritable from one generation to the next. And that theory then tells us if we actually want to do something about the evolutionary process and manipulate a change, and slow it in some way, then we have targets; we can hit one of those three major underpinnings -- the variation, the fitness link, or the heritability -- and by targeting them we can hope to begin to get a grip on these evolutionary arms races. So I think what's been said by everyone is that we're in a great place right now simply because evolution is beginning to be viewed as a proactive tool that we can apply in these important cases. And we can apply it much, much better if we understand it happens very quickly; [if we] understand that we really do, in a lot of cases, know how the evolutionary process works; and then understand there are ways that we can manipulate that.
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