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Tuesday, May 02, 2006

Better Drug-Producing Bacteria

A synthetically engineered strain of E. coli, stripped of non-essential parts, could boost the bug's industrial power.

By Emily Singer

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Leaner, meaner bacteria could provide safer and more efficient ways to make hard-to-manufacture biological products, including vaccines and DNA-based pharmaceuticals. In a paper published online in Science last week, researchers described how they used synthetic biology techniques to remove large, unnecessary chunks of the genome from Escherichia coli, a type of bacteria commonly used for research and industrial purposes. The resulting bacteria could grow just as well as their unedited counterparts and could produce some biological products more efficiently.

The findings show that genomes can be restructured on a large scale without harming the organism. That achievement points to the great promise of the emerging field of synthetic biology -- the attempt to design and rebuild organisms to perform specific functions. "It's a great achievement," says George Church, a geneticist at Harvard Medical School in Boston. "It makes people think about redoing genomes to make them do what you want it to do. It gives one hope that these sorts of things are possible."

Bacterial genomes change rapidly -- they have genetic elements that allow bits of DNA to move around the genome or to be swapped between other bacteria and viruses. This mechanism allows the bugs to adapt to different environments, such as high iron conditions, but it also means the bacteria hang on to genes that are unnecessary when grown in the lab.

To make the streamlined strain, researchers at the University of Wisconsin-Madison compared the genomes of different strains of bacteria to determine which genes were crucial for the organism's survival and which the bug could do without. They then removed these elements from the E. coli genetic code, making a smaller and more stable version of the bacteria. The new slimmed-down strain has about 15 percent less DNA. Scientists ultimately hope to remove another 5 percent.

One such disposable gene was the bug's swimming apparatus, which requires a lot of energy to make and manipulate. The extra genes "use up energy resources that could be better spent making a protein or whatever the product is," says Frederick Blattner, the geneticist who led the project. As a proof of principle, Blattner and colleagues showed that the new strain could produce a particular protein used in vaccines more efficiently than the common lab strain.

The bacteria could ultimately provide a better way to create DNA-based therapeutics, such as gene therapy. The idea of a reduced genome "is attractive from a safety and manufacturing point of view," says David Schoenhaut, director of technology affairs at Nucleonics, a biotech company based in Horsham, PA. For example, because the gene-swapping elements have been removed from the bacteria, the DNA region coding for the drug is unlikely to be inadvertently altered, which is an important safety concern.

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Comments

  • very dangerous technology because you never
    Guest (dan) on 05/02/2006 at 12:00 AM
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    know how these creatures will react with the environment.
    Rate this comment: 12345
    • Not overly so.
      Guest (Sean) on 05/02/2006 at 12:00 AM
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      Bacteria are among the most mutation-prone organisms on the planet, and you never know how *any* mutation is going to interact with the environment. As the article mentioned, it's not just random bits that flip with bacterial DNA, either; they can gain whole, pre-existing genetic sequences from other organisms.

      In this partuicular case, it's probably safer than most; they're taking stuff out, not putting it in. I'm not saying the absence of a gene can't make something harmful, but it's still lowering the total pool of what it can do, on a molecular level, rather than adding to it. This is particularly true here because they are actually removing traits that would enable it to survive outside the lab (such as the swimming apparatus).
      Rate this comment: 12345
  • E Coli working for pharaseuticals
    Guest (Robert Cooper) on 05/02/2006 at 12:00 AM
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    Excuse me for being a novice but I thought E Coli virus was one if not the most dangerous on Planet Earth!  Granted we can use things that seem bad to use them for good like nitro.  But how can we harness E. Coli to use it for good?  Isn't it a danger to our environment?
    Rate this comment: 12345
    • [no subject]
      Guest (Skeet) on 05/02/2006 at 12:00 AM
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      its the most deadly virus of them all!!!! Ludicris I say
      Rate this comment: 12345
    • [no subject]
      Guest on 05/02/2006 at 12:00 AM
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      Most e. coli aren't harmful - a rare strain called  E.coli O157:H7 is the one that causes health problems in humans. The strains used in research and manufacturing are the harmless variety.
      Rate this comment: 12345
    • E. coli isn't particularly dangerous
      Guest (Ed White) on 05/02/2006 at 12:00 AM
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      First: E. coli is a bacterium, not a virus.

      Second, as pointed out in this thread, only strain 0157:H57 is particularly dangerous.  In fact, almost all humans have E. coli in their digestive tract.

      I believe you have E. coli confused with the Ebola virus, which is an extremely dangerous pathogen.  Ebola-Marburg virus causes a hemorrhagic fever with an extremely high fatality rate - somewhere around 80%.
      Rate this comment: 12345
    • you'd be very sick without E Coli
      Guest (Leprechaun) on 05/03/2006 at 12:00 AM
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      The reason it's such a common lab bacterium is because you only need to wipe your butt to get some. They may be the most common of all the bacteria that live in people.
      Rate this comment: 12345
    • Idiots
      Guest (Nogg) on 05/04/2006 at 12:00 AM
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      You are dumb.  You and so many others like yourself make discussions of new technology so difficult.  E. Coli is a bacteria.  Bacteria and viruses are different things. 
      Rate this comment: 12345
  • Why it can be used for gene therapy?
    Guest (titus) on 05/07/2006 at 12:00 AM
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    1
    Rate this comment: 12345
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