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Author Topic:   Disabling Bacterial Resistance
gnojek
Inactive Member


Message 1 of 60 (210906)
05-24-2005 3:55 PM


Honestly, I don't know how much of a debate I can make out of this.

I just thought that this was an interesting article worth sharing.
It involves the discovery of the precise mechanism by which some bacteria are able to evolve resistance to certain antibiotics.

It shows (a) that mutations need not be caused by some random event and (b) that scientists sometimes actually do figure out the exact genetic mechanism by which organisms evolve.

Here is the article, which is really just an expose about a research article.

http://pubs.acs.org/cen/news/83/i20/8320notw1.html

quote:
Disabling Resistance
Inhibiting key protease prevents bacteria from evolving drug resistance

CELIA HENRY

Many antibiotics are rendered ineffective because bacteria become resistant to them. Now, a new study uncovers a potential therapeutic target for small-molecule drugs--a protease called LexA--that could stop bacteria from evolving resistance to antibiotics such as ciprofloxacin and rifampicin (PLoS Biol., published online May 10, dx.doi.org/10.1371/journal.pbio.0030176).

Drug resistance has been considered an inescapable outcome of mutations during genomic replication. It turns out, however, that spontaneous mutations aren't the main way that bacteria acquire resistance to ciprofloxacin.

Many people think that mutations are primarily due to mistakes during DNA replication despite the high fidelity of the process, but that's only a relatively minor route to mutations, says lead author Floyd E. Romesberg, assistant professor of chemistry at Scripps Research Institute. "Those rates are just too slow to be able to generate the number of mutations required for resistance."

In response to the stressful conditions created by antibiotics, bacteria instead turn to another mutation mechanism--part of the so-called SOS damage response--that is 10,000 times faster than normal genomic mutations. This system is usually turned on in response to DNA damage. Because quinolones such as ciprofloxacin work by interfering with enzymes that control the topology of DNA, they lead to DNA damage and may actually trigger the evolution of resistance.

The protease LexA is the gatekeeper of this alternative mutation pathway. As long as LexA remains intact, it represses the production of three DNA polymerases that are nonessential for genomic replication but required for mutations in response to DNA damage. Cleaving LexA allows those proteins to be produced and mutations to happen. Blocking LexA cleavage renders the bacteria unable to evolve resistance, making LexA a potential target for a small-molecule drug that could be administered in combination with the an tibiotic.

To test whether LexA is essential for mutations through SOS damage response, Romesberg and coworkers at Scripps and the University of Wisconsin Medical School, Madison, used a strain of Escherichia coli that couldn't cleave LexA. They grew the strain at antibiotic concentrations barely higher than the minimum necessary to work. If the strain could mutate, this condition made it as easy as possible to do so, Romesberg says. They found that the bacteria were not able to evolve resistance to ciprofloxacin or rifampicin, either in cell cultures or in a mouse model.

Disabling LexA "will be a highly novel approach to incapacitating bacteria to cope with the challenge of antibiotics. However, it is hard to predict what the consequence of such interference will be," says Shahriar Mobashery, a chemistry professor at the University of Notre Dame who studies bacterial resistance. "It will be interesting to see how this knowledge will be exploited in prolonging the usefulness of existing classes of antibiotics."

So far, the approach has been shown to work with antibiotics that directly damage DNA. "Even if it were only applicable to those drugs that directly damage DNA, it still hits the major market of antibiotics," Romesberg says. "If that were the case, I'm sort of okay with that." His group is now working to determine whether interfering with LexA also prevents bacteria from evolving resistance to other classes of antibiotics.



Let me know if the link to the original article works for you or not.

So, here's the deal: the trigger for the evolution of resistant bacteria is not random chance, but the antibiotic itself. The antibiotics damage bacterial DNA and repair mechanisms allow rapid mutation. The antibiotic also provides a rapid means of selection (the ones that didn't get beneficial mutations die off).

Anyway, I'd like to see if any creationists can explain bacterial resistance using scripture.


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AdminSylas
Inactive Member


Message 2 of 60 (211395)
05-26-2005 7:59 AM


Thread moved here from the Proposed New Topics forum.

This same research was recently introduced into discussion at Message 15, by Limbo, and there were some responses and discussion.

It is an interesting topic worthy of its own focussed thread, so I'm promoting anyway.

This message has been edited by AdminSylas, 05-26-2005 08:02 AM


  
zyncod
Inactive Member


Message 3 of 60 (211496)
05-26-2005 1:34 PM
Reply to: Message 1 by gnojek
05-24-2005 3:55 PM


Actually, the trigger is still random chance - the SOS response just ups the mutation rate. An analogy for this type of situation might be a person confronted by a tiger. The normal response to this situation would be to run like hell, even if there is only, say, a 1/1000 chance of getting away and you're likely going to hurt yourself just running anyway (smacking into things, etc). The SOS response is the bacterial equivalent of a 'panic' button.

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bugeater
Inactive Member


Message 4 of 60 (216596)
06-13-2005 10:26 AM
Reply to: Message 1 by gnojek
05-24-2005 3:55 PM


I'm wondering if this SOS response is a response to antibiotic treatment or to DNA damage. I suspect the latter.

If a bacterium has sustained a large amount of DNA damage (from whatever source), it would be helpful to activate a set of DNA polymerases that aren't so picky about error checking. A last resort if you will. A lot of these bacteria will probably die due to serious damage to important genes, but a few may get though, with an extremely high mutation rate. So the development of antibiotic resistance may just be a side effect of a simple survival mechanism rather than the whole purpose behind it.

A good test would be to see if this mechanism is activated by antibiotics that don't result in DNA damage.

However it isn't unusual that bacteria have evolved various defences against antibiotics. After all, microorganisms have been fighting amongst themselves for billions of years, and antibiotics are just some of the weapons they have been using. For example, a bacterium I worked on many years ago (Klebsiella planticola) naturally carried a beta-lactamase enzyme, which sole purpose is to defend against penicillin. Presumably it was exposed to penicillin in the wild, not from human intervention.

Marty


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randman 
Suspended Member (Idle past 4166 days)
Posts: 6367
Joined: 05-26-2005


Message 5 of 60 (216624)
06-13-2005 12:01 PM
Reply to: Message 1 by gnojek
05-24-2005 3:55 PM


This more in line with what you would expect from an ID perspective. The idea is that mutations are not random, but that there is an in-built code for activation and selection necessary to move the organism forward. It's fairly interesting.

Additionally, I think it's an error to assume randomnness in the type of mutation. In other words, this shows the frequency of mutation is not random, but governed by cirumstance. It may be that the type of mutation is not random either. Certainly, convergent DNA suggests that, and I would not be surprised to see that the DNA and organism are already programmed to trend in a certain direction in response to specific internal situations.


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nator
Member (Idle past 1437 days)
Posts: 12961
From: Ann Arbor
Joined: 12-09-2001


Message 6 of 60 (216627)
06-13-2005 12:20 PM
Reply to: Message 5 by randman
06-13-2005 12:01 PM


So, what experiment could be designed to show ID in such a situation with bacterial resistance?

What predictions would you make BEFORE the expeiment which could only be possible if an IDer was responsible?

IOW, design an experiment which eliminates the possibility that naturalistic mechanisms are responsible.


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mike the wiz
Member
Posts: 4721
From: u.k
Joined: 05-24-2003


Message 7 of 60 (216629)
06-13-2005 12:28 PM
Reply to: Message 6 by nator
06-13-2005 12:20 PM


I thought a good experiment is putting a species in a niche it's not used to. If the species dies off before it has a chance to evolve, then obviously morphological change takes too long to happen, but ex nihilo creation seems plausible. It seems an evolving food chain is more logical because of this, but we'll wait for what Brad has to say.

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randman 
Suspended Member (Idle past 4166 days)
Posts: 6367
Joined: 05-26-2005


Message 8 of 60 (216631)
06-13-2005 12:35 PM
Reply to: Message 6 by nator
06-13-2005 12:20 PM


couple of points

1. Naturalistic mechanisms can be ID.

2. It would be interesting to begin to test for QM effects, or other areas, to see if there is some principles and predetermined dispositions within the chemistry of the DNA.

As far as experiments, this experiment in the OP works nicely. It demonstrates non-randomness in mutations. Non-randmoness in mutations, is by definition, a move away from evolutionary models, and is indicative of design.

By the way, not saying one cannot claim that the non-randomness evolved as well, but the more you go back, you are going to, imo, find that the information and design is embedded in the process as a guiding force, and that a closer look at all the evidence in this light is warranted.


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nator
Member (Idle past 1437 days)
Posts: 12961
From: Ann Arbor
Joined: 12-09-2001


Message 9 of 60 (216639)
06-13-2005 12:55 PM
Reply to: Message 8 by randman
06-13-2005 12:35 PM


quote:
1. Naturalistic mechanisms can be ID.

How do you know when they are not ID?

This message has been edited by schrafinator, 06-13-2005 12:59 PM


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nator
Member (Idle past 1437 days)
Posts: 12961
From: Ann Arbor
Joined: 12-09-2001


Message 10 of 60 (216641)
06-13-2005 1:04 PM
Reply to: Message 7 by mike the wiz
06-13-2005 12:28 PM


quote:
I thought a good experiment is putting a species in a niche it's not used to. If the species dies off before it has a chance to evolve, then obviously morphological change takes too long to happen, but ex nihilo creation seems plausible.

Your experiment has been done many times both in the field and in the lab, and morphological change in species has been observed.

What do you conclude from this? That ID is falsified?


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mike the wiz
Member
Posts: 4721
From: u.k
Joined: 05-24-2003


Message 11 of 60 (216643)
06-13-2005 1:09 PM
Reply to: Message 10 by nator
06-13-2005 1:04 PM


Mikey's catch 22
Can you provide the link showing morphological change in species like the chimp or tiger or any species out of it's niche?

I don't recall a chimp growing wings any time soon.

That's because Mikey's catch 22 is valid. :) If they survive then they don't need evolution because no species has changed morphologically into another kind of animal, yet it has survived rendering the needed trait not needed. If they don't survive then evolution obviously doesn't happen because it's just not fast enough. :)

This message has been edited by mike the wiz, 06-13-2005 01:11 PM


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Wounded King
Member (Idle past 3362 days)
Posts: 4149
From: Edinburgh, Scotland
Joined: 04-09-2003


Message 12 of 60 (216644)
06-13-2005 1:13 PM
Reply to: Message 8 by randman
06-13-2005 12:35 PM


It demonstrates non-randomness in mutations. Non-randmoness in mutations, is by definition, a move away from evolutionary models, and is indicative of design.

Not really. It certainly demonstrates that mutation rates are tied in to the cellular environment and that an enzymatic change to that environment can affect the rate of mutation, but it doesn't mean that any specific mutation is occurring at a higher frequency so the position and nature of the mutation is still as random, in as much as it is stochastic, as ever.

Of course no one who is actually familiar with molecular genetics claims that mutations are completely random in frequency and character but we will elide over that strawman for the moment.

TTFN,

WK


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Trixie
Member (Idle past 2973 days)
Posts: 1011
From: Edinburgh
Joined: 01-03-2004


Message 13 of 60 (216683)
06-13-2005 3:53 PM
Reply to: Message 4 by bugeater
06-13-2005 10:26 AM


The SOS response
In bacteria the SOS response is the mechanism by which bacteria deal with DNA damage. That's how it is defined. It's also known as the error-prone repair mechanism because it makes quite a few mistakes and it therefore mismatches bases. It's hardly surpising that antibiotics which act by damaging DNA elicit the SOS rsponse. Radiation, including UV light, is the most common mechanism by which this damage is caused.

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nator
Member (Idle past 1437 days)
Posts: 12961
From: Ann Arbor
Joined: 12-09-2001


Message 14 of 60 (216691)
06-13-2005 5:49 PM
Reply to: Message 11 by mike the wiz
06-13-2005 1:09 PM


Re: Mikey's catch 22
quote:
Can you provide the link showing morphological change in species like the chimp or tiger or any species out of it's niche?

How about an iguana which has developed webbed feet and dives under the ocean to eat algae?

Or a squirrel that glides?

Or a bird that swims instead of flies, like a penguin?

Here's a more general listing of the evidence for morphological change. FYI, each of those names and dates in parenthese are peer-reviewed scientific papers that you can look up and read for yourself if you care to do the work:

http://www.talkorigins.org/faqs/comdesc/section5.htmllink

Prediction 5.2: Morphological change

Cladistic classification, and thus, phylogenetic reconstruction, is largely based on the various distinguishing morphological characteristics of species. Macroevolution requires that organisms' morphologies have changed throughout evolutionary history; thus, we should observe morphological change and variation in modern populations.

Confirmation:

There have been numerous observations of morphological change in populations of organisms (Endler 1986). Examples are the change in color of some organ, such as the yellow body or brown eyes of Drosophila, coat color in mice (Barsh 1996), scale color in fish (Houde 1988), and plumage pattern in birds (Morton 1990). Almost every imaginable heritable variation in size, length, width, or number of some physical aspect of animals has been recorded (Johnston and Selander 1973; Futuyma 1998, p. 247-262). This last fact is extremely important for common descent, since the major morphological differences between many species (e.g. species of amphibians, reptiles, mammals, and birds) are simple alterations in size of certain aspects of their respective parahomologous structures.


>

This message has been edited by schrafinator, 06-13-2005 06:16 PM


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zyncod
Inactive Member


Message 15 of 60 (216693)
06-13-2005 6:00 PM
Reply to: Message 13 by Trixie
06-13-2005 3:53 PM


Re: The SOS response
Not many antibiotics actually act by damaging DNA, but the point is valid. The only way that this type of SOS response could be said to be "intelligently designed" as opposed to evolving naturally, would be if a significant minority or a majority of bacteria could mutate a specific gene (ie, MDR) in response to an antibiotic that they do not encounter in nature (again, that would beg the question of WHY anybody would design bacteria that way, but we all know what the answer to this question would be).

This type of response is equivalent to the ability to form spores - a trait that has served the bacterial ancestors well in the past during times of great stress. This is a surprising finding but also fairly in line with common sense - the way a whole lot of discoveries in biology are.


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