Evolution of resistance–bacteria win again

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Resistance to antibiotics has been a concern of scientists almost since their widespread use began. In a 1945 interview with the New York Times, Alexander Fleming himself warned that the misuse of penicillin could lead to selection of resistant forms of bacteria, and indeed, he’d already derived such strains in the lab by varying doses of penicillin the bacteria were subjected to. A short 5 years later, several hospitals had reported that a majority of their Staph isolates were, as predicted, resistant to penicillin. This decline in effectiveness has led to a search for new sources and kinds of antimicrobial agents. One strategy involves going back to a decades-old approach researched by Soviet scientists: phage therapy. Here, they pit one microbe directly against another, using viruses called bacteriophage to infect, and kill, pathogenic bacteria. Vincent Fischetti at Rockefeller University has used this successfully to kill anthrax, Streptococcus pyogenes, and others. Another novel source of antibiotics has come from our own innate immune system, one of our initial defenses against microbial invaders.

An enormous variety of organisms produce compounds called cationic antimicrobial peptides. A component of our own innate immune system, these are fairly short strings of amino acids (less than 100 a.a.’s) that have a net positive charge. It is thought that these peptides work primarily by disrupting the integrity of the bacterial cell wall, essentially poking holes in the wall, causing death of the cell. Since the peptides are targeted at the bacterial cell wall structure, it was thought that resistance would require a fundamental change in membrane structure, making it an exceedingly rare event. Therefore, these antimicrobial peptides might make an excellent weapon in the fight against multiply drug-resistant bacteria. Additionally, the remarkable diversity of these peptides, combined with the presence of multiple types of peptides with different mechanisms of action present at the infection site, rendered unlikely the evolution of resistance to these molecules (or so the common thinking went). However, evolutionary biologists have pointed out that therapeutic use of these peptides would differ from natural exposure: concentration would be significantly higher, and a larger number of microbes would be exposed. Additionally, resistance to these peptides has been detailed in a few instances. For example, resistance to antimicrobial peptides has been shown to be essential for virulence in Staphylococcus aureus and Salmonella species, but we didn’t *witness* that resistance develop–therefore, it might simply be that those species have physiological properties that render them naturally resistant to many of these peptides, and were never susceptible in the first place.

Antimicrobial resistance is always a problem—it can render antibiotics much less useful, and make deadly infections almost untreatable. But resistance to these peptides could make us all vulnerable. The peptides of our innate immune system are one of our first lines of defense against an immense variety of pathogens, and we don’t know what the outcome may be if we compromise this essential level of protection. But realistically, could such resistance evolve within the bacterial population?

Dr. Michael Zasloff of Georgetown University was originally a doubter. In this 2002 Nature article, he states in conclusion:

Studies both in the laboratory and in the clinic confirm that emergence of resistance against antimicrobial peptides is less probable than observed for conventional antibiotics, and provides the impetus to develop antimicrobial peptides, both natural and laboratory conceived, into therapeutically useful agents.

Certainly in the short term, resistance was unlikely to evolve for the reasons I mentioned above. However, if these peptides are used over an extended period of time, could the mutations necessary to confer resistance accumulate? This was the question asked in a new study by Dr. Zasloff along with colleagues Gabriel Perron and Graham Bell. Following publication of his 2002 paper where he called evolution of resistance to these peptides “improbable,” Bell challenged Zasloff to test this theory. Zasloff took him up on the offer, and they’ve published their results in Proceedings of the Royal Society.

They tested this using strains of E. coli and Pseudomonas fluorescens. They started out growing these bacteria with low concentrations of a peptide antibiotic called pexiganan, a derivative of a peptide originally isolated from a frog. (Carl Zimmer has an excellent post on this same topic here). The experimental design was quite simple. They grew the bacteria, took a portion of the growth, and added that to a new tube with fresh media. Gradually, they increased the concentration of pexiganan in the growth medium. In all, they did 100 serial transfers of the bacteria (correlating to ~500-600 generations of bacteria), and the end result were–voilà!–bacterial populations that were resistant to the peptides.

Creationists/ID advocates (such as chemist Phil Skell) often claim that “evolutionary theory contributes little to experimental biology,” or that “evolution has little to do with almost all research in biology and biotechnology”, etc. etc. And sure, the theory of evolution didn’t *directly* result in the discovery of peptide antibiotics. But advances in biotechnology do not exist in a vacuum, and we have seen what can occur from the misapplication of these types of technologies, unguided by an understanding of underlying evolutionary principles. Peptide antibiotics have not yet been used clinically to treat human infections, but imagine if they had gone into widespread use without a thought given to the evolution of resistance to these peptides. Imagine if they had gone into widespread use prior to an investigation of the relatedness of various peptides to those produced by humans. Imagine if, as a result of not considering these implications, we had lost an ancient protection against bacteria—-which *evolved* over millions of years of host-pathogen interaction–due to a mere advancement in biotechnology. While I enjoy proving the evolution-doubters wrong, I hope it never comes down to that kind of situation in order to do so, and I hope this example is instructive to those who claim that evolution isn’t useful.

96 Comments

Strangely this example of evolution and the applied use of it is the one thing that will resonate louder in the minds of parents than any other belief, survival is natures greatest motor. Presented with the choice between a man in a white coat with a cure and a pulpit thumper the ranks of the blind sheep would thin very quickly. Somehow this message needs to be distilled and injected.

Presented with the choice between a man in a white coat with a cure and a pulpit thumper the ranks of the blind sheep would thin very quickly. Somehow this message needs to be distilled and injected.

Not to drag my own thread off-topic, but you might be surprised. Many people have been told so often that scientists are such evil “atheistic” materialists that they inherently distrust them, and value the word of their pastors over experts in the field. This has already happened with vaccination–while some parents are worried about thimerosal, others have objections on religious grounds, as fetal tissue has been used in the production of some vaccines.

Hey,

Would retiring an anti-biotic for a period of time (say 10-30 years), give enough time for bacteria to lose their immunity to the drug? I would think that the mechanisms (I’ve heard they’re selective pumps) to grant anti-biotic immunity would be an evolutionary disadvantage if none of that drug were present.

By giving evolution some time to select against the resistent strains we might be able to begin a program of cycling through antibiotics in a given order using a defined period of use to ensure that we never run out of them.

Blog problems.

Normally its the technicalterms or challenging concepts that make it hard for me to fully understand an article. But Tara has a hot picture on the top right of her blog that lowers my IQ to room temperature. Thanks Tara.

*twiddles pen, awkwardly*

Tara wrote, “Not to drag my own thread off-topic, but you might be surprised. Many people have been told so often that scientists are such evil “atheistic” materialists that they inherently distrust them, and value the word of their pastors over experts in the field. This has already happened with vaccination—while some parents are worried about thimerosal, others have objections on religious grounds, as fetal tissue has been used in the production of some vaccines.” And this is happening in Amish communities in the Midwest, where children have contracted polio: http://www.nytimes.com/2005/11/08/n[…]08polio.html Oddly enough, polio is never reported in societies where vaccinations are mandated; but in the Amish communities, where modern medicine is suspect and innoculation is rejected, these “dead” diseases reappear. Maybe the Amish are feeling god’s wrath? : )

I’m a geologist and not a biologist, so my grasp on biology literature is very poor.

Would anybody be able to recommend some references that show:

1) somebody mapping the genome of some bacteria 2) letting populations of that bacteria grow for many generations 3) remapping the genome of that bacteria to see where mutations in the DNA occurred 4) even better, said mutations enhance the survivability of the bacteria in certain environments

I am familiar with Richard Lenk’s E. Coli experiments, but would like some more documentation to peruse if there is any.

Would retiring an anti-biotic for a period of time (say 10-30 years), give enough time for bacteria to lose their immunity to the drug? I would think that the mechanisms (I’ve heard they’re selective pumps) to grant anti-biotic immunity would be an evolutionary disadvantage if none of that drug were present.

By giving evolution some time to select against the resistent strains we might be able to begin a program of cycling through antibiotics in a given order using a defined period of use to ensure that we never run out of them.

That has been tried to some extent, with mixed results. There’s a review of some of the literature here, which basically concludes that we need more research on the topic.

The fact that bacteria evolve resistance to antibiotics just shows how marvelously well-designed they are. In fact, designing a system that is capable of evolving requires more intelligence and sophistication than designing a static system. It cracks me up how you fundies think it is such a big deal that bacteria evolve. (“Evolve” is a strong word for it – they do, after all, remain not only bacteria, but practically the same kind of bacteria.)

Fundamentalist Darwinian: “What?! You don’t believe that the bat and the whale are close cousins and that this grizzly bear’s many-greats-grandpappy was a fish? Well, I’ll prove it to you: bacteria have been known to evolve resistance to antibiotics. So there.”

Give me a break.

I see you missed the entire point of my post, but thank you for your comments.

The fact that bacteria evolve resistance to antibiotics just shows how marvelously well-designed they are. In fact, designing a system that is capable of evolving requires more intelligence and sophistication than designing a static system. It cracks me up how you fundies think it is such a big deal that bacteria evolve. (“Evolve” is a strong word for it — they do, after all, remain not only bacteria, but practically the same kind of bacteria.)

Fundamentalist Darwinian: “What?! You don’t believe that the bat and the whale are close cousins and that this grizzly bear’s many-greats-grandpappy was a fish? Well, I’ll prove it to you: bacteria have been known to evolve resistance to antibiotics. So there.”

Give me a break.

The level of ignorance you just demonstrated is amazing. But I bet it won’t stop you from taking those ‘fundamentalist Darwinian’ medicines next time you have the flu, will you?

Miguelito,

Would anybody be able to recommend some references that show:

1) somebody mapping the genome of some bacteria 2) letting populations of that bacteria grow for many generations 3) remapping the genome of that bacteria to see where mutations in the DNA occurred 4) even better, said mutations enhance the survivability of the bacteria in certain environments

There are 2 big roadblocks to many of us carrying out studies like that: 1) time and 2) money. Even with short generation times, it takes awhile to get them up to a significant number of generations, and then finding single nucleotide changes in a bacterium which may have a genome of 2-5 million base pairs or so is very challenging for those of us with small lab budgets. I can’t think of anything like that offhand, but I’ll do a lit search when I get a chance and see what I can find.

Thanks, but I’ll take medicines that are well grounded in science.

they do, after all, remain not only bacteria, but practically the same kind of bacteria

This raises some interesting questions about “kinds.” How many bacterial “kinds” are there? And, “practically”? I wasn’t aware there was any wiggle room at all in the “kinds” to allow for qualification. Are they the same “kind” after the resistance has evolved, or aren’t they? How do we tell?

theonomo Wrote:

Fundamentalist Darwinian: “What?! You don’t believe that the bat and the whale are close cousins and that this grizzly bear’s many-greats-grandpappy was a fish? Well, I’ll prove it to you: bacteria have been known to evolve resistance to antibiotics. So there.”

In which the poster invokes what I call the Pee Wee Herman Argument (I know you are, but what am I? in referring to rational people as “fundamentalist”) and proves once again that it’s impossible to tell the difference between a well-constructed parody of creationist “logic” and the real thing.

Evolve” is a strong word for it — they do, after all, remain not only bacteria, but practically the same kind of bacteria.)

A strong word?? So, you’d only call it ‘evolution’ if they spontaneously changed into, say, raccoons, overnight?

The fact that bacteria evolve resistance to antibiotics just shows how marvelously well-designed they are. In fact, designing a system that is capable of evolving requires more intelligence and sophistication than designing a static system

So let me get this straight. You admit that bacteria evolve. But you claim that this evolving proves that they’re designed. And therefore this proves evolution is false.

That’s one of the most ridiculous, self-referential attempts at ‘logic’ I’ve seen in years. Beautiful.

Thanks, but I’ll take medicines that are well grounded in science.

Good for you. Next time you get sick, make sure the scientists who designed it didn’t believe in evolution. Can’t be too careful, you know.

How many bacterial “kinds” are there?

Many.

And, “practically”? I wasn’t aware there was any wiggle room at all in the “kinds” to allow for qualification.

Yes, there is wiggle room. They aren’t exactly the same – just practically the same. Maybe you should heighten your awareness of these matters.

Are they the same “kind” after the resistance has evolved, or aren’t they?

They are practically the same kind.

This raises some interesting questions about “kinds.” How many bacterial “kinds” are there? And, “practically”? I wasn’t aware there was any wiggle room at all in the “kinds” to allow for qualification. Are they the same “kind” after the resistance has evolved, or aren’t they? How do we tell?

I’m sure Theonomo doesn’t know the answer to any of these questions, but since they are ‘kinds’ one must assume they were all on Noah’s ark.

I’m sure Theonomo doesn’t know the answer to any of these questions, but since they are ‘kinds’ one must assume they were all on Noah’s ark.

I don’t believe in the literal truth of that whole Noah’s ark story. Thanks for trying to pigeon-hole me, though.

They are practically the same kind.

define “practically”

Theonomo,

The reason scientists so often cite bacteria is that bacteria go through so many generations in so short a time, that evolution can be easily observed with them. However, this isn’t the only observation of evolution and speciation, the observation has been made for higher organisms as well. Have you browsed through the TalkOrigins website?

The communication problem seems to stem from a conceptual problem. People who reject evolution cannot imagine why microevolution would lead to macroevolution, and macroevolution is the only way they define evolution. The only remedy to that is to do some work and read about what the theory of evolution says. If it still doesn’t make sense, ask more questions and read more.

People at PT will usually make fun of you, unless you are asking a sincere question. Be specific in your question. Just by coming up with a specific question, you’re halfway to understanding.

Ask “how many,” get told “many.” Realize you’re probably talking to a creationist. Maybe you should heighten your awareness of these matters. Should I start with Genesis? Because I’m pretty sure there’s no mention of bacteria. Or do you have a more authoritative source on bacterial “kinds” in mind?

Tara Smith Wrote:

There are 2 big roadblocks to many of us carrying out studies like that: 1) time and 2) money. Even with short generation times, it takes awhile to get them up to a significant number of generations, and then finding single nucleotide changes in a bacterium which may have a genome of 2-5 million base pairs or so is very challenging for those of us with small lab budgets. I can’t think of anything like that offhand, but I’ll do a lit search when I get a chance and see what I can find.

Thanks, I’d appreciate that. I wouldn’t know where to start on my own lit search on the topic: I’m trapped by my ignorance of biochemical technospeak.

Even smaller scale studies (where they focus on only a relatively few genes) would be appreciated.

define “practically”

prac·ti·cal·ly (prktk-l) adv.

1. In a way that is practical. 2. For all practical purposes; virtually. 3. All but; nearly; almost.

lol. right… so now explain how it works in the terms you use it in.

like several have already asked you.

why be a troll?

did you ignore what Katarina posted?

Should I start with Genesis? Because I’m pretty sure there’s no mention of bacteria.

Or do you have a more authoritative source on bacterial “kinds” in mind?

Maybe you should try a textbook.

“I see you missed the entire point of my post, but thank you for your comments.”

You’ve been playing with creationists too long. Absence of evidence of understanding does not imply missunderstanding. I got the point, but you get drawn to the topright hand corner of your blog.

*shrug*

Heh. Rich, that wasn’t directed at you. And I’m sure if it’s ever so distracting, a post-it note would cover up the pic just fine. :)

theonomo, I’d be very happy to address any concerns/questions you have about evolution, and I’m sure others would do the same. I much prefer to have real discussion rather than sniping.

I am well aware that as soon as anyone on this board expresses an opinion that does not fall in line with the Official Story that is handed down by the Darwinian Priesthood they will be ridiculed. No big deal. I just like to express my thoughts on these matters once in a while.

By the way, the debating techniques used on here are typical of Darwinian fundamentalists: mention that you don’t think that the fact that bacteria evolve resistance to antibiotics is good evidence for macro-evolution and next thing you know you are being asked to deliniate all the different kinds of bacteria that have ever existed. It’s the “quick – swamp him with requests for irrelevant details that will take him hours to figure out” defense.

But you haven’t expressed any “thoughts;” you’ve called names and started with the ridicule yourself. How about we start over and you post your valid criticisms, and we’ll forget all the “kinds” stuff.

theonomo Wrote:

I am well aware that as soon as anyone on this board expresses an opinion that does not fall in line with the Official Story that is handed down by the Darwinian Priesthood they will be ridiculed. No big deal. I just like to express my thoughts on these matters once in a while.

You’re certainly free to express your thoughts. But what we’d like to see is intelligent discussion. To enable that, we need more than opinion, we need data and rational argument. If you have them, we’d like to see them. But simply questioning something with no supporting logic, or making blatantly incorrect statements about science will tend, I admit, to get you banged on the head with a stuffed eel-skin. Partly it’s simply irritation at the same valueless arguments. We’d be delighted with something new and interesting.

By the way, the debating techniques used on here are typical of Darwinian fundamentalists:

Sorry, there are no Darwin fundamentalists here. There may be some in the world, but I’ve yet to see one post on this site. The posters I’ve seen here accept evolution as the best current explanation to fit the facts - nothing more. New evidence, new arguments, new paradigms could overturn that acceptance. Give it a try!

mention that you don’t think that the fact that bacteria evolve resistance to antibiotics is good evidence for macro-evolution and next thing you know you are being asked to delineate all the different kinds of bacteria that have ever existed. It’s the “quick — swamp him with requests for irrelevant details that will take him hours to figure out” defense.

No, it’s the “produce some evidence for this claim”. As I say, we’re so eager to find something really novel and supported to discuss that we get a little overenthusiastic. Sorry about that.

Don’t know if this would fit on a T-Shirt and isn’t a “pro-evolution” saying, but it IS funny :) :

Thou shalt not covet thy neighbor’s wife, his lamb thou shalt not slaughter, thank Heavens there is no Commandment, about coveting thy neighbor’s daughter!

Renier Wrote:

Just interesting, from a local newspaper report

Interesting. I think peptide antibiotics would be a better way to go, but we’ll have to see. I hate it when people say stuff like this, though:

Cipla Medpro medical director Dr Nic de Jongh said the key difference from antibiotics was that lactic acid bacteria were already present in the body, which meant they were definitely safe.

Bah. Yes, commensals are usually our friends. But just because something is “already present in the body,” it doesn’t mean it’s “definitely safe” ! Many of us carry Staph aureus and Strep pyogenes, but they’re not “definitely safe.” Just my annoyance…

lactic acid bacteria were already present in the body, which meant they were definitely safe.

Stomach acid isn’t even “safe” in the esophagus. Just because matter is “safe” in isolation in the body doesn’t mean it’s safe in general.

Well, it’s a good thing that they seem clear on the scientific method, therefore clearly state that lots of testing still needs to be done. Just think, if ID people did this it would be “Something designed the peptides to be used by humans, and since the designer is intelligent we can ASSUME it is safe. Bring the needle!” :-)

Question. What are the odds that we will start finding bacteria strains that learns (evolves) to resist the peptides?

Sir_ToeJam Wrote:

t-shirt slogans

How about ‘Darth Darwin’ or ‘Darth Darwin’s Apprentice’ I like ‘ID Scientit’ as well (nice fundie typo that)

Question. What are the odds that we will start finding bacteria strains that learns (evolves) to resist the peptides?

That’s really hard to say. A lot would likely depend on how they’d be used–if they were saved as a kind of “last line of defense,” it might take a long time. Or there may be some out there already that are resistant, and could transfer this to others, making them all but useless in no time. But odds are good that at *some* point if they’re used commercially, resistance will appear.

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This page contains a single entry by Tara Smith published on November 15, 2005 3:55 AM.

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