# Is Genetic Engineering of Antibiotics Possible?

**URL:** <https://boards.straightdope.com/t/is-genetic-engineering-of-antibiotics-possible/653044>\
**Category:** Factual Questions\
**Created:** [March 15, 2013, 9:17pm UTC](https://boards.straightdope.com/t/is-genetic-engineering-of-antibiotics-possible/653044 "2013-03-15T21:17:14Z")\
**Posts on this page:** 19\
**Page:** 1

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**Author:** ![ralph124c](https://avatars.discourse-cdn.com/v4/letter/r/8797f3/32.png) [@ralph124c](https://boards.straightdope.com/u/ralph124c)\
**Post date:** [March 15, 2013, 9:17pm UTC](https://boards.straightdope.com/t/is-genetic-engineering-of-antibiotics-possible/653044/1 "2013-03-15T21:17:14Z")

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Now that physicians are seeing antibiotic-resistant bacteria, finding new treatments for these diseases is a pressing problem. I heard that no major new broad-spectrum antibiotics have been developed since about 1986. So, could existing strains of say, penicillin be genetically modified, so as to deal with these new bacteria strains? And, if we are unable to find new and effective antibiotics, what is our next line of defense (in dealing with these new disease germs)?

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**Author:** ![leahcim](https://avatars.discourse-cdn.com/v4/letter/l/b4bc9f/32.png) [@leahcim](https://boards.straightdope.com/u/leahcim)\
**Post date:** [March 15, 2013, 9:39pm UTC](https://boards.straightdope.com/t/is-genetic-engineering-of-antibiotics-possible/653044/2 "2013-03-15T21:39:28Z")

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You might be able to genetically engineer some modified version of the penicillium fungus (or any other organism) to synthesize a different chemical, but penicillin itself is just a chemical with no genetic code to modify. I.e. there’s no “mutant penicillin” that might be effective on penicillin-resistant bacteria.

As for things that could be used instead of antibiotics, [phage therapy](http://en.wikipedia.org/wiki/Phage_therapy) is an option.

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**Author:** ![Vlad\_Igor](https://avatars.discourse-cdn.com/v4/letter/v/7feea3/32.png) [@Vlad\_Igor](https://boards.straightdope.com/u/Vlad_Igor)\
**Post date:** [March 15, 2013, 10:00pm UTC](https://boards.straightdope.com/t/is-genetic-engineering-of-antibiotics-possible/653044/3 "2013-03-15T22:00:29Z")

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There are several classes of drugs, the beta-lactams being one of them. The first known beta-lactam was penicillin, and other analogues, based on the core molecular structure have been developed. Other beta-lactam antibiotics include piperacilin, amoxacillin and ampicillin.

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**Author:** ![si\_blakely](https://avatars.discourse-cdn.com/v4/letter/s/d9b06d/32.png) [@si\_blakely](https://boards.straightdope.com/u/si_blakely)\
**Post date:** [March 16, 2013, 6:59pm UTC](https://boards.straightdope.com/t/is-genetic-engineering-of-antibiotics-possible/653044/4 "2013-03-16T18:59:13Z")

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The problem has been that pharmaceutical companies don’t see a profit in developing new antibiotics - they are expensive to develop, and will only be used as a drug of last resort for a short periods of time. It will even be hard to have large scale trials, as the infections that they will be used to treat are still very rare (and if they are not rare, the bacterial apocalypse will be upon us and it will be too late). New funding and testing solutions will be required.

As for genetic engineering, understanding how **bacteria** work at a genetic level may provide new insights into how best to combat them without hitting the resistance barrier.

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**Author:** ![Canadjun](https://avatars.discourse-cdn.com/v4/letter/c/76d3ee/32.png) [@Canadjun](https://boards.straightdope.com/u/Canadjun)\
**Post date:** [March 16, 2013, 7:28pm UTC](https://boards.straightdope.com/t/is-genetic-engineering-of-antibiotics-possible/653044/5 "2013-03-16T19:28:29Z")

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> [@ralph124c](#):
>
> Now that physicians are seeing antibiotic-resistant bacteria, finding new treatments for these diseases is a pressing problem. I heard that no major new broad-spectrum antibiotics have been developed since about 1986. So, could existing strains of say, penicillin be genetically modified, so as to deal with these new bacteria strains? And, if we are unable to find new and effective antibiotics, what is our next line of defense (in dealing with these new disease germs)?

In the case of penicillin and related antibiotics, they have developed a drug ([Clavulanic acid](http://en.wikipedia.org/wiki/Clavulanic_acid)) that isn’t an antibiotic per se, but blocks bacterial defense against those antibiotics. I just had a prescription of Amoxiclav for a nasty bladder infection, which is amoxicillin+clavulanic acid (that’s why I knew what to google). Hopefully similar strategies can be developed for other antibiotics.

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**Author:** ![Smeghead](https://avatars.discourse-cdn.com/v4/letter/s/f1d935/32.png) [@Smeghead](https://boards.straightdope.com/u/Smeghead)\
**Post date:** [March 16, 2013, 9:22pm UTC](https://boards.straightdope.com/t/is-genetic-engineering-of-antibiotics-possible/653044/6 "2013-03-16T21:22:33Z")

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Ralph, we haven’t relied on microorganisms to make our antibiotics for us for a long, long time. True, bacteria and fungi have been the original sources where we first discovered many antibiotics, but actually making them has been done in the lab for a long, long time. And for almost exactly as long a time, chemists have been making variations on the original antibiotic molecules to come up with new antibiotics. So what you’re proposing is what we have been doing for decades already, except that you’ve included the unnecessary step of using actual organisms as our factories.

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**Author:** ![JWT\_Kottekoe](https://avatars.discourse-cdn.com/v4/letter/j/3ec8ea/32.png) [@JWT\_Kottekoe](https://boards.straightdope.com/u/JWT_Kottekoe)\
**Post date:** [March 16, 2013, 10:20pm UTC](https://boards.straightdope.com/t/is-genetic-engineering-of-antibiotics-possible/653044/7 "2013-03-16T22:20:12Z")

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Yes, it is possible and it is an active area of research. See for example:

[Synthetic Biology of Antibiotic Production](http://www.esf.org/index.php?id=7241)

> [@](#):
>
> This conference will focus on the advancement of synthetic biology, especially its application in the field of antibiotic production in filamentous fungi and actinomycete bacteria, including the implementation and modification of complex biosynthesis pathway modules in existing and new production hosts. Antibiotics production is regulated by complex networks and involves intricate multi-step biosynthetic machineries, as well as major reorganization of primary metabolic fluxes to redirect cellular metabolic resources towards their biosynthesis. The urgent need for new antibiotics caused by the accelerating emergence of multi-drug resistant pathogens worldwide has led to a strong interest in the research community for decidedly novel approaches.

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**Author:** ![DSeid](https://sea3.discourse-cdn.com/straightdope/user_avatar/boards.straightdope.com/dseid/32/20194_2.png) [@DSeid](https://boards.straightdope.com/u/DSeid)\
**Post date:** [March 16, 2013, 10:46pm UTC](https://boards.straightdope.com/t/is-genetic-engineering-of-antibiotics-possible/653044/8 "2013-03-16T22:46:55Z")

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[One example.](http://oregonstate.edu/ua/ncs/archives/2011/apr/bioengineered-antibiotic-could-lead-lifesaving-malaria-therapies)

> [@](#):
>
> The natural form of pactamycin occurs in soil bacteria. It attacks not only protozoa such as the mosquito-borne P. falciparum, which causes malaria, but also bacteria, viruses and tumors. Unfortunately, it attacks healthy cells in mammals, as well. In an effort to capture pactamycin’s benefits while eliminating or minimizing its detriments, OSU researchers modified the genetic structure of the microbe that produces the antibiotic by inactivating or “knocking out” certain genes. They tested the new versions – called “analogues” – on human colorectal cancer cells.
> 
> “The results revealed that the new analogues are significantly less toxic than pactamycin,” said Mahmud, a medicinal chemist in the OSU College of Pharmacy. … “The study resulted in a number of pactamycin analogues that showed potent antimalarial activity but, in contrast to pactamycin, have reduced cytotoxicity against mammalian cells.”

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**Author:** ![Vitalis\_Kissmeoff](https://avatars.discourse-cdn.com/v4/letter/v/f05b48/32.png) [@Vitalis\_Kissmeoff](https://boards.straightdope.com/u/Vitalis_Kissmeoff)\
**Post date:** [March 17, 2013, 12:48am UTC](https://boards.straightdope.com/t/is-genetic-engineering-of-antibiotics-possible/653044/9 "2013-03-17T00:48:32Z")

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Rumors of using viruses to combat the bugs, supposedly that’s what scientists were working on before striking gold with Pen.

Anyone know if nano technology offers hope?

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**Author:** ![sweat209](https://avatars.discourse-cdn.com/v4/letter/s/9fc348/32.png) [@sweat209](https://boards.straightdope.com/u/sweat209)\
**Post date:** [March 17, 2013, 5:17am UTC](https://boards.straightdope.com/t/is-genetic-engineering-of-antibiotics-possible/653044/10 "2013-03-17T05:17:54Z")

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> [@ralph124c](#):
>
> Now that physicians are seeing antibiotic-resistant bacteria, finding new treatments for these diseases is a pressing problem. I heard that no major new broad-spectrum antibiotics have been developed since about 1986. So, could existing strains of say, penicillin be genetically modified, so as to deal with these new bacteria strains? And, if we are unable to find new and effective antibiotics, what is our next line of defense (in dealing with these new disease germs)?

I think the problem is not so much finding new antibiotic drugs but they find new drugs but antibiotic-resistant is happening faster than they find new drugs.

May be more research into infections disease will allow faster new drugs.

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<div class="post-metadata">

**Author:** ![si\_blakely](https://avatars.discourse-cdn.com/v4/letter/s/d9b06d/32.png) [@si\_blakely](https://boards.straightdope.com/u/si_blakely)\
**Post date:** [March 17, 2013, 7:27am UTC](https://boards.straightdope.com/t/is-genetic-engineering-of-antibiotics-possible/653044/11 "2013-03-17T07:27:21Z")

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> [@sweat209](#):
>
> I think the problem is not so much finding new antibiotic drugs but they find new drugs but antibiotic-resistant is happening faster than they find new drugs.

It is true that resistance to antibiotics of last resort is evolving and spreading very fast.

However, pharmaceutical companies have not spent money on developing new antibiotics (as I said in my previous post) because any new effective antibiotics will automatically be restricted to use as a treatment of last resort - expensive and rarely used. It has to be, otherwise it will become the next antibiotic that cannot be used because of resistance.

8 major pharmaceutical companies have stopped development of antibiotics in the last 20 years, including Pfizer. You need regulatory agencies to allow smaller trials, as you cannot have a large scale one for infections like Carbapenem Resistant Enterobacteriacea, or MRSA. There just are not that many cases, which is a good thing.

The latest New Scientist magazine has a good summary of the problems.

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**Author:** ![Busy\_Scissors](https://avatars.discourse-cdn.com/v4/letter/b/d78d45/32.png) [@Busy\_Scissors](https://boards.straightdope.com/u/Busy_Scissors)\
**Post date:** [March 18, 2013, 11:04am UTC](https://boards.straightdope.com/t/is-genetic-engineering-of-antibiotics-possible/653044/12 "2013-03-18T11:04:05Z")

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> [@Smeghead](#):
>
> Ralph, we haven’t relied on microorganisms to make our antibiotics for us for a long, long time. True, bacteria and fungi have been the original sources where we first discovered many antibiotics, but actually making them has been done in the lab for a long, long time. And for almost exactly as long a time, chemists have been making variations on the original antibiotic molecules to come up with new antibiotics. So what you’re proposing is what we have been doing for decades already, except that you’ve included the unnecessary step of using actual organisms as our factories.

Nearly all the penicillins and cephalosporins are produced by microbial fermentation. Some will require one or two synthetic steps post fermentation but all of the synthetic heavy lifting is handled by the bug - we do literally rely on the microorganism to produce this principal class of antibiotic.

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**Author:** ![DSeid](https://sea3.discourse-cdn.com/straightdope/user_avatar/boards.straightdope.com/dseid/32/20194_2.png) [@DSeid](https://boards.straightdope.com/u/DSeid)\
**Post date:** [March 18, 2013, 12:01pm UTC](https://boards.straightdope.com/t/is-genetic-engineering-of-antibiotics-possible/653044/13 "2013-03-18T12:01:54Z")

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> [@si\_blakely](#):
>
> … You need regulatory agencies to allow smaller trials, as you cannot have a large scale one for infections like Carbapenem Resistant Enterobacteriacea, or MRSA. There just are not that many cases, which is a good thing. …

Meh. There are plenty of cases, especially of MRSA. And you still need to know if something works and if it is safe. Anyway the issue is that the pot of gold for pharmas is not in a new improved antibiotic, used a few days at a time infrequently until the buggers learn their ways around it too, it’s in a new medicine someone needs to take every day for the rest of their long life. Rationally the wiser investment for a large for-profit company is not in antibiotics. This is one area where market forces fail to address a societal need.

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**Author:** ![Anaglyph](https://avatars.discourse-cdn.com/v4/letter/a/ed8c4c/32.png) [@Anaglyph](https://boards.straightdope.com/u/Anaglyph)\
**Post date:** [March 18, 2013, 1:23pm UTC](https://boards.straightdope.com/t/is-genetic-engineering-of-antibiotics-possible/653044/14 "2013-03-18T13:23:10Z")

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> [@Vitalis\_Kissmeoff](#):
>
> Rumors of using viruses to combat the bugs, supposedly that’s what scientists were working on before striking gold with Pen.  
> Anyone know if nano technology offers hope?

Bacteriophages (viruses that infect bacteria) have been investigated in this way. However, these are not “broad band” - you need to know very precisely which bacterial strain causes the infection to fight it with a specific type of phages. In contrast, most classical antibiotics target biochemical processes that are common for a wide range of bacteria, such as cell wall synthesis or bacterial protein synthesis.

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**Author:** ![ralph124c](https://avatars.discourse-cdn.com/v4/letter/r/8797f3/32.png) [@ralph124c](https://boards.straightdope.com/u/ralph124c)\
**Post date:** [March 18, 2013, 3:33pm UTC](https://boards.straightdope.com/t/is-genetic-engineering-of-antibiotics-possible/653044/15 "2013-03-18T15:33:46Z")

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Well, since bacteria acquire resistance (to antibiotics) through mutation, genetic modification of the antibiotic ought to keep the desirable (anti-bacterial) action of the specific antibiotic. So when we are able to identify the specific gene that gives the bacteria immunity, we can change the genome of the antibiotic to keep it useful.

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**Author:** ![Frylock](https://avatars.discourse-cdn.com/v4/letter/f/ce7236/32.png) [@Frylock](https://boards.straightdope.com/u/Frylock)\
**Post date:** [March 18, 2013, 3:43pm UTC](https://boards.straightdope.com/t/is-genetic-engineering-of-antibiotics-possible/653044/16 "2013-03-18T15:43:18Z")

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> [@ralph124c](#):
>
> Well, since bacteria acquire resistance (to antibiotics) through mutation, genetic modification of the antibiotic ought to keep the desirable (anti-bacterial) action of the specific antibiotic. So when we are able to identify the specific gene that gives the bacteria immunity, we can change the genome of the antibiotic to keep it useful.

Antibiotics do not have genomes.

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**Author:** ![md2000](https://avatars.discourse-cdn.com/v4/letter/m/73ab20/32.png) [@md2000](https://boards.straightdope.com/u/md2000)\
**Post date:** [March 18, 2013, 5:36pm UTC](https://boards.straightdope.com/t/is-genetic-engineering-of-antibiotics-possible/653044/17 "2013-03-18T17:36:32Z")

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Antibiotics are basically chemicals. Typically they interfere with the life cycle or reproductive processes of bacteria - or at least, more so than with large organisms. An infecting bacteria that cannot reproduce faster that the white blood cells kill it is going to lose the battle ASAP. If you can actually kill the bacteria, so much the better.

In order to do this, the antibiotic has to exploit some difference in the biochemical processes between bacteria and humans (or large animals). The “trick” is to find these exploitable diferences.

Another modern trick is to combine antibiotics. Like the aforementioned _Amoxiclav_ you combine two chemicals in the hope that abcteria find it that much harder to simultaneously develop resistance to two different attacks.

So the problem is not “modifying” the organisms that produce antibiotics, the trick is to figureout what ways to modify them. Over the eons some fungus or mold, for example, developed a chemical to protect themselves from bacteria - much as some plants have evolved to have a really bad taste or smell to stop animals from eating them. In both situations, it’s a chicken-and-egg thing; for example, as the animals became more tolerant of say, sour leaves when they were really hungry, only the plants with the most awful tasting leaves survived, and they became the norm.

That particular configuration - antibacterial mold or sour plants - took a lot of evolutionary “trial and error” to find the right chemical mix. It’s not something that happens overnight. Unfortunately, we’ve done the opposite to bacteria - we dose them often and everywhere with antibiotics; often, people don’t finish the full treatment, and a few hardy types survive, the ones that are most resistant. After a few decades, we kill off the least resistant all over the world - all that’s left is the resistant ones. If we wanted to _make_ resistant bacteria, we could not have done it much better.

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<div class="post-metadata">

**Author:** ![Canadjun](https://avatars.discourse-cdn.com/v4/letter/c/76d3ee/32.png) [@Canadjun](https://boards.straightdope.com/u/Canadjun)\
**Post date:** [March 18, 2013, 5:42pm UTC](https://boards.straightdope.com/t/is-genetic-engineering-of-antibiotics-possible/653044/18 "2013-03-18T17:42:59Z")

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> [@ralph124c](#):
>
> Well, since bacteria acquire resistance (to antibiotics) through mutation, genetic modification of the antibiotic ought to keep the desirable (anti-bacterial) action of the specific antibiotic. So when we are able to identify the specific gene that gives the bacteria immunity, we can change the genome of the antibiotic to keep it useful.

Try googling a few antibiotics - e.g. [Ampicillin](http://en.wikipedia.org/wiki/Ampicillin), [Keflex](http://en.wikipedia.org/wiki/Cefalexin), [ciprofloxacin](http://en.wikipedia.org/wiki/Ciprofloxacin). They all show molecular structures of the antibiotics. No DNA or RNA in any of them, so no [genome](http://en.wikipedia.org/wiki/Genome).

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<div class="post-metadata">

**Author:** ![DSeid](https://sea3.discourse-cdn.com/straightdope/user_avatar/boards.straightdope.com/dseid/32/20194_2.png) [@DSeid](https://boards.straightdope.com/u/DSeid)\
**Post date:** [March 18, 2013, 7:47pm UTC](https://boards.straightdope.com/t/is-genetic-engineering-of-antibiotics-possible/653044/19 "2013-03-18T19:47:22Z")

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> [@md2000](#):
>
> Another modern trick is to combine antibiotics. Like the aforementioned _Amoxiclav_ you combine two chemicals in the hope that abcteria find it that much harder to simultaneously develop resistance to two different attacks. …

A point of clarification – clavulanic acid does not actually attack an organism at all. The major resistance to the beta-lactams (like Amoxiciilin) has been that bacteria produce an enzyme, beta-lactamase, that breaks the antibiotic down. Clavulanic acid binds to that enzyme, preventing it from attacking the antibiotic, and thereby restoring its efficacy.

For those interested, [this](http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2189988/) is a pretty good review of antibiotic development approaches, up to date as of 2007 anyway. And I’m not aware of too much progress since then.
