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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.


Replies to this message:
 Message 3 by zyncod, posted 05-26-2005 1:34 PM gnojek has taken no action
 Message 4 by bugeater, posted 06-13-2005 10:26 AM gnojek has replied
 Message 5 by randman, posted 06-13-2005 12:01 PM gnojek has replied
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gnojek
Inactive Member


Message 23 of 60 (216865)
06-14-2005 4:53 PM
Reply to: Message 5 by randman
06-13-2005 12:01 PM


randman writes:

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.


I don't see how to differentiate between "random" and "victim of circumstance."

It's the same thing.

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.

Forward toward what?

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gnojek
Inactive Member


Message 24 of 60 (216873)
06-14-2005 5:05 PM
Reply to: Message 17 by bugeater
06-13-2005 10:24 PM


Re: The SOS response
hanks for that Trixie. It is as I expected. So in reality it is the antibiotic that is causing the damage, not the SOS response

From what I understand, the class of antibiotics studied did not mutate DNA. They disrupted DNA gyrases and polymerases, which caused mutations in the DNA.

Anyway, I guess this is still a classic case of mutation and natural selection in action.

My bad.


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gnojek
Inactive Member


Message 26 of 60 (216894)
06-14-2005 5:35 PM
Reply to: Message 4 by bugeater
06-13-2005 10:26 AM


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.

This is very interesting.

A mold produces an antibiotic compound to battle off bacteria that may eat it or its food source.

But a species of bacteria developed a weapon against that.

It's like a bio-arms race.


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