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Thread: Super E. coli to the rescue.

  1. #1 Super E. coli to the rescue. 
    Moderator Moderator Cogito Ergo Sum's Avatar
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    The concept of using bacteria to suppress the growth of other bacteria is not a new method in the world of medicine.
    For example, researchers (Krüger, C. et al., 2002) used modified L. zeae bacteria to reduce caries in rat models.

    However, in this case they used E. coli to kill Pseudomonas aeruginosa. The latter is a pathogenic bacterium that causes i.a. pneumonia.
    Although this was already done in 2011, they changed the mechanisms. Mark Peplow reports:
    "Synthetic biologist Matthew Chang at Nanyang Technological University in Singapore has armed Escherichia coli bacteria with a ‘seek and kill’ system that targets cells of Pseudomonas aeruginosa, an invasive bacterium that causes pneumonia and other illnesses. In preliminary tests with infected mice, the modified bacterium left a trail of dead P. aeruginosa in its wake.
    Chang and his team had previously developed an E. coli that could brew up an antibacterial peptide called pyocin, and then explode to release its deadly cargo whenever it detected a chemical signal emitted by its prey. Now the bioengineered vigilante is back — and it is tougher than ever."


    This 'seek and kill' is constructed as followed:
    1. They inserted the DNA sequence of the bullet in the genome of the E.coli. This bullet (called MccS) is specific, i.e. it only kills pathogens.
    2. Next, they inserted the DNA sequence of DNA nuclease I. This product can 'chew' through the protective envelop (called biofilm) that holds the pathogens together.
    3. The pathogens often measure their own population. This is done by a messenger molecule, which is picked up by a protein of E. coli.
    4. The messenger molecule and the protein bind and give the E.coli the signal to 'swim' towards the direction from which the messenger came (this movement is called chemotaxis).
    5. As E.coli arrives, it produces the bullets and P. aeruginosa loses the battle.



    This method is promising, although human trials have to be designed to prove its true effectiveness.

    What do you think?


    Sources:
    Krüger, C. et al. (2002), "In situ delivery of passive immunity by lactobacilli producing single-chain antibodies", Nature Biotechnology 20, pp. 702-706
    Engineered bacterium hunts down pathogens : Nature News & Comment


    Last edited by Cogito Ergo Sum; April 24th, 2014 at 02:00 PM. Reason: Spelling error.
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    Forum Masters Degree LuciDreaming's Avatar
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    I am immensely interested in progress of bacterial treatments on a personal level - I certainly think that these show promise. However having first hand experience of what can happen just by messing about with bacteria I am cautious about how we go about not disturbing an individuals microbiome too much or at least ensure it returns to normal afterwards. On the other hand....on a personal level I really really want them to hurry up and make bacterial therapies common place too......


    "And we should consider every day lost on which we have not danced at least once. And we should call every truth false which was not accompanied by at least one laugh" Nietzsche.
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    Is the chemotactic molecule specific to P. aeruginosa?
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    Quote Originally Posted by mat5592 View Post
    Is the chemotactic molecule specific to P. aeruginosa?

    According to the abstract, it is:
    "The reprogrammed E. coli degraded the mature biofilm matrix and killed the latent cells encapsulated within by expressing and secreting the antimicrobial peptide microcin S and the nuclease DNaseI upon the detection of quorum sensing molecules naturally secreted by P. aeruginosa."


    I do not know what the name is of these quorum sensing molecules, since I cannot access the study.


    Source:

    Reprogramming microbes to be a pathogen-seeking killer - ACS Synthetic Biology (ACS Publications)
    "The only safe rule is to dispute only with those of your acquaintance of whom you know that they possess sufficient intelligence and self-respect not to advance absurdities; to appeal to reason and not to authority, and to listen to reason and yield to it; and, finally, to be willing to accept reason even from an opponent, and to be just enough to bear being proved to be in the wrong."

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    Quote Originally Posted by Cogito Ergo Sum View Post
    Quote Originally Posted by mat5592 View Post
    Is the chemotactic molecule specific to P. aeruginosa?

    According to the abstract, it is:
    "The reprogrammed E. coli degraded the mature biofilm matrix and killed the latent cells encapsulated within by expressing and secreting the antimicrobial peptide microcin S and the nuclease DNaseI upon the detection of quorum sensing molecules naturally secreted by P. aeruginosa."


    I do not know what the name is of these quorum sensing molecules, since I cannot access the study.


    Source:

    Reprogramming microbes to be a pathogen-seeking killer - ACS Synthetic Biology (ACS Publications)
    Looks like we won't find out, either. $35 for 48 hours of access to the study?!
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    Quote Originally Posted by mat5592 View Post
    $35 for 48 hours of access to the study?!

    It must be a study with a high impact factor.

    Luckily, the number of open-access articles is increasing.
    (cf. Open Access versus Payment.)
    "The only safe rule is to dispute only with those of your acquaintance of whom you know that they possess sufficient intelligence and self-respect not to advance absurdities; to appeal to reason and not to authority, and to listen to reason and yield to it; and, finally, to be willing to accept reason even from an opponent, and to be just enough to bear being proved to be in the wrong."

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    Quote Originally Posted by Cogito Ergo Sum View Post
    Quote Originally Posted by mat5592 View Post
    $35 for 48 hours of access to the study?!

    It must be a study with a high impact factor.

    Luckily, the number of open-access articles is increasing.
    (cf. Open Access versus Payment.)
    That's wonderful news, Cogito
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    Hey, that sounds really cool. But, I am slightly skeptical about introducing GM bacteria into the environment. In this antibiotic scare, scientists have learned a lot about how bacteria communicate and how they exchange genetic information. My fear is that introducing E. coli containing a modification that causes them to target and kill other cells might backfire. That is, what if a certain pathogenic GI tract bacteria picked up those introduced genes and then proceeded to severely out-compete all other bacteria in the gut? Then a GI pathogen would be much more severe: the natural competition in the gut would be eliminated by inadvertently giving a pathogen an advantage.
    Check out my blog!! www.iRNAbooks.weebly.com
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    Quote Originally Posted by iRNAblogger View Post
    Hey, that sounds really cool. But, I am slightly skeptical about introducing GM bacteria into the environment. In this antibiotic scare, scientists have learned a lot about how bacteria communicate and how they exchange genetic information. My fear is that introducing E. coli containing a modification that causes them to target and kill other cells might backfire. That is, what if a certain pathogenic GI tract bacteria picked up those introduced genes and then proceeded to severely out-compete all other bacteria in the gut? Then a GI pathogen would be much more severe: the natural competition in the gut would be eliminated by inadvertently giving a pathogen an advantage.

    Good point.
    This is certainly an issue that must be incorporated into investigations when scientists set up human medical trials.
    However, it might be possible to make transduction between GI tract bacteria unlikely; this was achieved in another study (Steidler, L. et al., 2003).
    "The only safe rule is to dispute only with those of your acquaintance of whom you know that they possess sufficient intelligence and self-respect not to advance absurdities; to appeal to reason and not to authority, and to listen to reason and yield to it; and, finally, to be willing to accept reason even from an opponent, and to be just enough to bear being proved to be in the wrong."

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    In a related note, these researchers are using viruses (bacteriophages) to target and kill bacteria (particularly Clostridium difficile in this case). I've seen lots of research over the past couple years using modified bacteria, viruses, and leukocytes to treat things like cancer and bacterial infections as opposed to traditional medicines. Anyone else think these approaches could be promising?

    Bacteria-eating viruses 'magic bullets in the war on superbugs'
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    Quote Originally Posted by mat5592 View Post
    In a related note, these researchers are using viruses (bacteriophages) to target and kill bacteria (particularly Clostridium difficile in this case). I've seen lots of research over the past couple years using modified bacteria, viruses, and leukocytes to treat things like cancer and bacterial infections as opposed to traditional medicines. Anyone else think these approaches could be promising?

    Bacteria-eating viruses 'magic bullets in the war on superbugs'

    Yes, I too have noticed such a trend. It is as if the field of medicine is focusing on molecular biological therapies that are more personal.

    I have not yet looked into the use of leukocytes or modified organisms to battle cancer, but this article looks promising, especially this phrase:
    "The key advantage of using phages over antibiotics lies in their specificity. A phage will infect and kill only a specific strain/species of bacteria. This is particularly important when treating conditions like C. diff infections, where maintenance of the natural balance of gut bacteria greatly reduces the chance of relapse."


    However, I could not find how they were going to administer these phage mixtures into human patients.
    "The only safe rule is to dispute only with those of your acquaintance of whom you know that they possess sufficient intelligence and self-respect not to advance absurdities; to appeal to reason and not to authority, and to listen to reason and yield to it; and, finally, to be willing to accept reason even from an opponent, and to be just enough to bear being proved to be in the wrong."

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    Quote Originally Posted by Cogito Ergo Sum View Post
    Quote Originally Posted by mat5592 View Post
    In a related note, these researchers are using viruses (bacteriophages) to target and kill bacteria (particularly Clostridium difficile in this case). I've seen lots of research over the past couple years using modified bacteria, viruses, and leukocytes to treat things like cancer and bacterial infections as opposed to traditional medicines. Anyone else think these approaches could be promising?

    Bacteria-eating viruses 'magic bullets in the war on superbugs'

    I have not yet looked into the use of leukocytes or modified organisms to battle cancer
    Here is an example:

    Leukemia patients remain in remission more than two years after engineered T cell therapy
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    Thank you for sharing this article!

    I had to read the article a few times before I understood what the protocol was.
    Nonetheless, it seems to be an effective (and clever) way of battling leukemia.
    "The only safe rule is to dispute only with those of your acquaintance of whom you know that they possess sufficient intelligence and self-respect not to advance absurdities; to appeal to reason and not to authority, and to listen to reason and yield to it; and, finally, to be willing to accept reason even from an opponent, and to be just enough to bear being proved to be in the wrong."

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