Pharmaceutical Metabolites in Wastewater

Originally posted by bsl4doc

... it is not due to antibiotic RESISTANCE, so much as antibiotic METABOLISM.

Do you think bacteria are antibiotic resistant because they have adapted and evolved to metabolize antibiotics? ...As the result of sustained exposure?

Very interesting find, by the way. I liked that article.

The whole series is very good - and easy for everyone to understand.


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Do you think bacteria are antibiotic resistant because they have adapted and evolved to metabolize antibiotics? ...As the result of sustained exposure?

See, that's the crux of the issue. It's sort of a chicken or the egg argument for most doctors I know. On the one hand, bacteria are known to evolve in response to their environment. On the other hand, when a new drug is devised, we find bacteria already resistant to it to some extent before it is commerically released. This tells me, as well as a few colleagues, that perhaps, since many drugs are variations on forms found in nature, that many of these bacteria pick up non-specific resistances to certain chemicals in nature. I don't know if you are familiar with the concept of a haptene, but it's basically a small piece of an offending molecule, be it a heavy metal, pollen, etc, which normally does not produce an antibody response, but when bound to a carrier protein, the cell can recognize it as an antigen and produce an antibody. This antibody can then work against the haptene in the future, even when the molecule is not bound to a carrier protein. I see this as a key element to bacterial antibiotic resistance. At some point, a haptene conformer of some relative of penicillin was introduced to an organism, not bacteria, but an organism, and it created an immune response. This DNA coding for the immune response may be somehow linked to bacteria "learning" to resist antibiotics. There have been plenty of cases in which cross-species DNA sharing has occured between bacteria and hosts on pure chance, mostly due to a lysed host cell releasing DNA, so I don't see why this couldn't have happened.

~MFP

Originally posted by bsl4doc

Do you think bacteria are antibiotic resistant because they have adapted and evolved to metabolize antibiotics? ...As the result of sustained exposure?

...On the one hand, bacteria are known to evolve in response to their environment. ...There have been plenty of cases in which cross-species DNA sharing has occured between bacteria and hosts on pure chance, mostly due to a lysed host cell releasing DNA, so I don't see why this couldn't have happened.

So - you agree that evolution is a multifactorial process. Do you also agree that exposure to antibiotics may be a factor that triggers antibiotic resistance in bacteria?

Or not?



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So - you agree that evolution is a multifactorial process. Do you also agree that exposure to antibiotics may be a factor that triggers antibiotic resistance in bacteria?

Or not?

No, I don't entirely agree with the idea that the antibiotics trigger resistance. Bacteria do not create DNA out of nothing. Some bacteria somewhere made a point mutation that allowed it to withstand the effects of penicillin. This bacteria had a bit of a survival edge on the other similar bacteria, and through conjugation and selection passed this DNA on. The exposure to antibiotics did not trigger this. The antibiotic is a selective tool, killing off the non-resistant bacteria and allowing the resistant strain to use the newly available nutrients to further colonize areas.

~MFP

Here is an interesting description worth reading:

The basis of microbial resistance to antibiotics

Inherent (Natural) Resistance. Bacteria may be inherently resistant to an antibiotic. For example, a streptomycete has some gene that is responsible for resistance to its own antibiotic; or a Gram-negative bacterium has an outer membrane that establishes a permeability barrier against the antibiotic; or an organism lacks a transport system for the antibiotic; or it lacks the target or reaction that is hit by the antibiotic.

Acquired Resistance. Bacteria can develop resistance to antibiotics, e.g. bacterial populations previously-sensitive to antibiotics become resistant. This type of resistance results from changes in the bacterial genome. Acquired resistance is driven by two genetic processes in bacteria: (1) mutation and selection (sometimes referred to as vertical evolution); (2) exchange of genes between strains and species (sometimes called horizontal evolution).

Vertical evolution is strictly a matter of Darwinian evolution driven by principles of natural selection: a spontaneous mutation in the bacterial chromosome imparts resistance to a member of the bacterial population. In the selective environment of the antibiotic, the wild type (non mutants) are killed and the resistant mutant is allowed to grow and flourish. The mutation rate for most bacterial genes is approximately 10-8. This means that if a bacterial population doubles from 108 cells to 2 x 108 cells, there is likely to be a mutant present for any given gene. Since bacteria grow to reach population densities far in excess of 109 cells, such a mutant could develop from a single generation during 15 minutes of growth.

Horizontal evolution is the acquisition of genes for resistance from another organism. For example, a streptomycete has a gene for resistance to streptomycin (its own antibiotic), but somehow that gene escapes and gets into E. coli or Shigella. Or, more likely, Some bacterium develops genetic resistance through the process of mutation and selection and then donates these genes to some other bacterium through one of several processes for genetic exchange that exist in bacteria.

Bacteria are able to exchange genes in nature by three processes: conjugation, transduction and transformation. Conjugation involves cell-to-cell contact as DNA crosses a sex pilus from donor to recipient. During transduction, a virus transfers the genes between mating bacteria. In transformation, DNA is acquired directly from the environment, having been released from another cell. Genetic recombination can follow the transfer of DNA from one cell to another leading to the emergence of a new genotype (recombinant). It is common for DNA to be transferred as plasmids between mating bacteria. Since bacteria usually develop their genes for drug resistance on plasmids (called resistance transfer factors, or RTFs), they are able to spread drug resistance to other strains and species during genetic exchange processes.

The combined effects of fast growth rates, high concentrations of cells, genetic processes of mutation and selection, and the ability to exchange genes, account for the extraordinary rates of adaptation and evolution that can be observed in the bacteria. For these reasons bacterial adaptation (resistance) to the antibiotic environment seems to take place very rapidly in evolutionary time: bacteria evolve fast!

Bacterial resistance to Antibiotics

Clear as mud.

[edit on 24-3-2006 by loam]

Loam-

The source describes the rate of mutation in a somewhat unclear and almost incorrect fashion. When I was an undergrad, I was a paid assistant for the Microbiology professor. We kept strains of E. coli on constant culture, both resistant and non resistant strains. Every so often, we would cross culture them to check for mutants. In our fairly large populations sizes, a resistant mutant, also called a reversion if dealing with resistant to nonresistant changes, would only show up about once every 3 or 4 months, and even that was too often according to the professor. Considering the number of base pairs in a bacterial genome and the rarity of a mutation occuring, can you imagine how likely it is for that one mutant that occurs every few months will be a mutation that confers resistance?

~MFP

Originally posted by bsl4doc

In our fairly large populations sizes, a resistant mutant, also called a reversion if dealing with resistant to nonresistant changes, would only show up about once every 3 or 4 months, and even that was too often according to the professor.

Did the environment change? Or were conditions constant?

One would expect changes in a constantly changing environment, but stable conditions should preclude mutation. ...If your professor thought one mutant every 3 or 4 months was too much, I assume the environment was stable. Unlike the earth's natural -and polluted- environment.

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True, the environment we were working with was stable. However, given the large number of years we're talking about here in relation to the sudden rise in cases of antibiotic resistant bacteria, I don't think you can attribute any sudden changes to the mutation. Any changes were small. How long have antibiotics been around, especially penicillin and its derivatives? A VERY long time, so why would we just be seeing these mutants in the last 15 or 20 years as a prevalent threat? Also, why did these strains exist even before the massive dispersion of penicillin drugs, which they did? Doesn't this hint at perhaps some natural source of epitopic antigen conferring resistance to individuals in the bacterial population?

Sorry if any of this is confusing or written poorly in English...some of my fellows and I went out for a rare night on the town to celebrate and thoroughly enjoyed ourselves, heh.

~MFP

[edit on 3/25/2006 by bsl4doc]

Originally posted by bsl4doc
True, the environment we were working with was stable.

Which is why your professor thought a mutant every 3 or 4 months was a lot. One expects mutants in unstable environments, but not when conditions are stable.

...given the large number of years we're talking about here in relation to the sudden rise in cases of antibiotic resistant bacteria, I don't think you can attribute any sudden changes to the mutation. Any changes were small. How long have antibiotics been around, especially penicillin and its derivatives? A VERY long time, so why would we just be seeing these mutants in the last 15 or 20 years as a prevalent threat?

Hmmm.

"Discovered initially by a French medical student, Ernest Duchesne, in 1896, and then rediscovered by Scottish physician Alexander Fleming in 1928, the product of the soil mold Penicillium crippled many types of disease-causing bacteria. But just four years after drug companies began mass-producing penicillin in 1943, microbes began appearing that could resist it."

New antibiotics were developed because microbes became rapidly resistant - and the circle went round and round. It is not a new phenomenon.

What's new is that we're out of ammunition. There are few new antibiotics in the pike - but lots of resistant bacteria.

Also, why did these strains exist even before the massive dispersion of penicillin drugs, which they did? Doesn't this hint at perhaps some natural source of epitopic antigen conferring resistance to individuals in the bacterial population?

Yes. Penicillin is a naturally occurring soil mould. Both the mould and bacteria likely continue to evolve in the natural environment - in response to each other and to other factors.


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Originally posted by soficrow
"Discovered initially by a French medical student, Ernest Duchesne, in 1896, and then rediscovered by Scottish physician Alexander Fleming in 1928, the product of the soil mold Penicillium crippled many types of disease-causing bacteria. But just four years after drug companies began mass-producing penicillin in 1943, microbes began appearing that could resist it."

New antibiotics were developed because microbes became rapidly resistant - and the circle went round and round. It is not a new phenomenon.

What's new is that we're out of ammunition. There are few new antibiotics in the pike - but lots of resistant bacteria.

I came across the same explanation in several sources. You saved me the time of going back to hunt for them.

Soficrow, you said that penicillin mold and bacteria evolved with each other. Wouldn't that assume that at some point the bacteria may have picked up resistance to it BEFORE it was discovered as a medication?

~MFP

Originally posted by bsl4doc
Soficrow, you said that penicillin mold and bacteria evolved with each other. Wouldn't that assume that at some point the bacteria may have picked up resistance to it BEFORE it was discovered as a medication?

Exactly my point.

...and to follow the logic - the penicillin and bacteria would continue to co-evolve in a natural environment and resistance would seesaw in nature. Much as bacteriophages and bacteria do.

...in a sense, we arrested penicillin's evolutionary process by manufacturing a fixed "recipe," and prevented it from evolving in response to bacteria's evolved resistance.

Point being, nothing in nature is static. Only in the lab - and even then, not reliably stable.

...and to follow the logic - the penicillin and bacteria would continue to co-evolve in a natural environment and resistance would seesaw in nature. Much as bacteriophages and bacteria do.

...in a sense, we arrested penicillin's evolutionary process by manufacturing a fixed "recipe," and prevented it from evolving in response to bacteria's evolved resistance.

Point being, nothing in nature is static. Only in the lab - and even then, not reliably stable.

You raise a very good and viable point, Sofi. The only thing keeping me from saying you're completely right is the speed at which bacteria are becoming resistant to new drugs. If the bacteria take so long to mutate randomly, why would they suddenly be able to make directed mutations?

~MFP

Originally posted by bsl4doc

...in a sense, we arrested penicillin's evolutionary process by manufacturing a fixed "recipe," and prevented it from evolving in response to bacteria's evolved resistance.

You raise a very good and viable point, Sofi. The only thing keeping me from saying you're completely right is the speed at which bacteria are becoming resistant to new drugs. If the bacteria take so long to mutate randomly, why would they suddenly be able to make directed mutations?

Because they learned to metabolize the stuff. Bacteria mutated to use antibiotics as food. Beautifully efficient. Not unprecedented I don't think...