Notices
Results 1 to 8 of 8

Thread: Alternative Antibacterial Methods: A Proposal.

  1. #1 Alternative Antibacterial Methods: A Proposal. 
    Moderator Moderator Cogito Ergo Sum's Avatar
    Join Date
    Jun 2013
    Location
    Belgium
    Posts
    2,519
    Over the course of a few months, I created threads[1][2][3] about new discoveries in the field of antibiotics and participated in several other threads about the same subject. In one of those threads, I posed this question:

    (cf. post #6)
    Should science seek novel antibiotics to treat these multidrug resistant pathogens or should science focus on other therapies (e.g. phage therapy and morpholino oligomers), in your opinion? After all, clinical screening, development and human testing of a novel antibiotic is expensive and time-consuming.

    This question has remained unanswered up to now, but I am willing to change that.
    I want to research what the possible benefits are of other antibacterial methods (e.g. phage therapy, PPMOs, metallopolymers,...).

    In extenso, the scope of my research is to assess:

    1. how antibiotic resistance is acquired and
    2. how it poses a threat on global human health and
    3. how it can be reduced and
    4. if reduction can be partially achieved by using existent antibiotics and/or novel antibacterial methods and
    5. if those new methods are better than the classic compounds based on the production costs, efficacy (in vivo) and safety (i.e. side effects).



    This is solely a proposal (hence the title), not an actual scheme for a scientific paper as I doubt I am capable of writing that.
    Nonetheless, I am interested in your opinions, suggestions and criticisms.


    Last edited by Cogito Ergo Sum; April 27th, 2014 at 10:58 AM.
    "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."

    ~ Arthur Schopenhauer, The Art of Being Right: 38 Ways to Win an Argument (1831), Stratagem XXXVIII.
    Reply With Quote  
     

  2.  
     

  3. #2  
    Forum Professor Zwolver's Avatar
    Join Date
    May 2006
    Location
    Netherlands
    Posts
    1,667
    1; Antibacterial resistance is mainly the ability to block the antibiotics to start dissolving the cell wall or to stop preventing it from forming more cell wall to duplicate. So any system that goes around regular formation of the cell wall, or a different combination of substances inside it, will provide antibiotic resistance. Another (slightly less resistant but more like hazard control) method is by creating a protein that simply destroys the antibiotics, while not being immune to its effects.

    2; Very obvious. Our enemy now has flak jackets, so we must shoot armor piercing antibiotics at it.

    3; How it can be reduced... Well my own thoughts about this, is creating a less effective, antibiotics that works on large groups of bacteria. Why less effective? Well, for one, that it won't be used by idiots (doctors) in hospitals to treat everything with, and will only be fully understood by professionals. This bacterium, because of the purely synthetic nature of this drug, will not know it, and thus can not form a resistance to it so quickly. Also, because it works less well, it may not cause extinctions, and merely reduce growth. In combination with the natural healing ability of the human body, this new drug can give the body another day to fight off the disease, which is usually enough to form an actual resistance to it. Also, because it works less well, but no resistance to it, it may be economical for pharmaceutical companies to consider it.

    4; Yes and no, existing antibiotics have been gathered from bacteria, fungi, archea, algae and some higher plants. Which have been competing with bacteria for millions of years, so there is bound to be some that have formed a resistance to it. But using multiple antibiotics will still kill off a small percentage of the bacteria who don't have the plasmid.

    5; Can't name one.. will look for a new method, however the one i discribed would be a nice way. Actually feeding bacteria a supplement, then attacking the supplement could be another way of killing the bacteria.

    I will look into this.. but i think i may just stumble onto colloidal silver with this..


    Growing up, i marveled at star-trek's science, and ignored the perfect society. Now, i try to ignore their science, and marvel at the society.

    Imagine, being able to create matter out of thin air, and not coming up with using drones for boarding hostile ships. Or using drones to defend your own ship. Heck, using drones to block energy attacks, counterattack or for surveillance. Unless, of course, they are nano-machines in your blood, which is a billion times more complex..
    Reply With Quote  
     

  4. #3  
    Moderator Moderator Cogito Ergo Sum's Avatar
    Join Date
    Jun 2013
    Location
    Belgium
    Posts
    2,519
    Quote Originally Posted by Zwolver View Post
    1; Antibacterial resistance is mainly the ability to block the antibiotics to start dissolving the cell wall or to stop preventing it from forming more cell wall to duplicate. So any system that goes around regular formation of the cell wall, or a different combination of substances inside it, will provide antibiotic resistance. Another (slightly less resistant but more like hazard control) method is by creating a protein that simply destroys the antibiotics, while not being immune to its effects.

    Such as a bacterium producing -lactamase to destroy penicillin?

    2; Very obvious. Our enemy now has flak jackets, so we must shoot armor piercing antibiotics at it.

    I second that.

    3; How it can be reduced... Well my own thoughts about this, is creating a less effective, antibiotics that works on large groups of bacteria. Why less effective? Well, for one, that it won't be used by idiots (doctors) in hospitals to treat everything with, and will only be fully understood by professionals. This bacterium, because of the purely synthetic nature of this drug, will not know it, and thus can not form a resistance to it so quickly. Also, because it works less well, it may not cause extinctions, and merely reduce growth. In combination with the natural healing ability of the human body, this new drug can give the body another day to fight off the disease, which is usually enough to form an actual resistance to it. Also, because it works less well, but no resistance to it, it may be economical for pharmaceutical companies to consider it.

    In essence, you are proposing a bacteriostatic compound, rather than a bacteriocidal one?
    I was also thinking about the causes of antibiotic resistance (apart from environmental pressure) and how to reduce them, e.g. transport of people and food, lateral gene transfer, inappropriate usage of antibiotics, etc.

    4; Yes and no, existing antibiotics have been gathered from bacteria, fungi, archea, algae and some higher plants. Which have been competing with bacteria for millions of years, so there is bound to be some that have formed a resistance to it. But using multiple antibiotics will still kill off a small percentage of the bacteria who don't have the plasmid.

    I do not understand what you state there. Could you rephrase it?


    5; Can't name one.. will look for a new method, however the one i discribed would be a nice way. Actually feeding bacteria a supplement, then attacking the supplement could be another way of killing the bacteria.

    I will look into this.. but i think i may just stumble onto colloidal silver with this.

    The usage of i.a. metal ions (e.g. colloidal silver) seems promising, but we have to take possible side effects of those metal ions into consideration.
    The cooperation of classic antibiotics and metallopolymers to fight off MRSA is promising in vitro, but the effect on animal and human health is currently uncertain.
    "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."

    ~ Arthur Schopenhauer, The Art of Being Right: 38 Ways to Win an Argument (1831), Stratagem XXXVIII.
    Reply With Quote  
     

  5. #4  
    Making antisense Jon Moulton's Avatar
    Join Date
    Oct 2013
    Location
    Corvallis, Oregon, USA
    Posts
    51
    A disadvantage of the PPMO technology is that it will be very expensive compared to current antibiotics. An advantage of the technology is that it can be targeted rapidly to new genotypes of bacteria and there are no known physiological resistance mechanisms to PPMOs (though if a target sequence is not sufficiently conserved, a strain could mutate that sequence to escape PPMO susceptibility).
    Reply With Quote  
     

  6. #5  
    Moderator Moderator Cogito Ergo Sum's Avatar
    Join Date
    Jun 2013
    Location
    Belgium
    Posts
    2,519
    Quote Originally Posted by Jon Moulton View Post
    A disadvantage of the PPMO technology is that it will be very expensive compared to current antibiotics. An advantage of the technology is that it can be targeted rapidly to new genotypes of bacteria and there are no known physiological resistance mechanisms to PPMOs (though if a target sequence is not sufficiently conserved, a strain could mutate that sequence to escape PPMO susceptibility).

    It would seem that specificity is great advantage, as I assume that you can design the PPMOs as such that they do not harm the human microbiome.
    However, is it not so that the development of new antibiotics is very expensive, which might be the cause why the number of clinical released antibiotics is declining since 1991?

    According to pharmaceutical industry estimates, about 7 million candidate compounds must be screened to yield a single useful clinical drug. Drugs effective in the laboratory must then be tested for efficacy and toxicity in animals and finally in clinical trials in humans. Animal testing requires multiple trials over several years to ensure that the candidate drug is both effective and safe. Clinical trials in humans to check efficacy and safety take additional years for each drug. Each year, the pharmaceutical industry spends up to $4 billion on new antimicrobial drug development. Discovery and development for each drug typically takes 10-25 years before it is approved for clinical use. The cost of discovery and development, from the laboratory through clinical trials, is estimated at over $500 million for each drug approved for human use. This is a major reason why pharmaceutical drugs are so expensive.

    Source:
    Madigan, M., Martinko, J., Stahl, D. et al. (2012), "Brock Biology of Microorganisms, 13th Edition", Pearson, p. 810
    "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."

    ~ Arthur Schopenhauer, The Art of Being Right: 38 Ways to Win an Argument (1831), Stratagem XXXVIII.
    Reply With Quote  
     

  7. #6  
    Making antisense Jon Moulton's Avatar
    Join Date
    Oct 2013
    Location
    Corvallis, Oregon, USA
    Posts
    51
    Antibiotic development is expensive. However, production of traditional antibiotics is much simpler than PPMOs, which are synthetic ~10 kiloDalton molecules. It is production cost instead of development cost that will be the main barrier to PPMO adoption; the per-dose costs will remain high even if total volume increases. In some cases Morpholino-based drug costs may be acceptable, such as for the Duchenne muscular dystrophy drug now in clinical trials. As an emergency treatment for a massively multitude-resistant deadly pathogenic bacterial strain, peptide-conjugated Morpholinos might be similarly deemed cost-effective.
    Reply With Quote  
     

  8. #7  
    Moderator Moderator Cogito Ergo Sum's Avatar
    Join Date
    Jun 2013
    Location
    Belgium
    Posts
    2,519
    Quote Originally Posted by Jon Moulton View Post
    Antibiotic development is expensive. However, production of traditional antibiotics is much simpler than PPMOs, which are synthetic ~10 kiloDalton molecules. It is production cost instead of development cost that will be the main barrier to PPMO adoption; the per-dose costs will remain high even if total volume increases. In some cases Morpholino-based drug costs may be acceptable, such as for the Duchenne muscular dystrophy drug now in clinical trials. As an emergency treatment for a massively multitude-resistant deadly pathogenic bacterial strain, peptide-conjugated Morpholinos might be similarly deemed cost-effective.

    Yet, if the clinical trials demonstrate that PPMOs are effective against DMD, will that not lead to more investments into better equipment to produce those synthetic molecules?
    "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."

    ~ Arthur Schopenhauer, The Art of Being Right: 38 Ways to Win an Argument (1831), Stratagem XXXVIII.
    Reply With Quote  
     

  9. #8  
    Making antisense Jon Moulton's Avatar
    Join Date
    Oct 2013
    Location
    Corvallis, Oregon, USA
    Posts
    51
    Quote Originally Posted by Cogito Ergo Sum View Post
    Yet, if the clinical trials demonstrate that PPMOs are effective against DMD, will that not lead to more investments into better equipment to produce those synthetic molecules?
    Economies of scale should make lower prices possible as subunit synthesis becomes less expensive per-unit. However, this is still a 70+ step synthesis under GMP conditions. If oligos shorter than 25-mers are used, this will further decrease synthetic/regulatory costs, and antibacterial Morpholinos are usually made shorter than 25 bases.
    Reply With Quote  
     

Similar Threads

  1. Testing Antibacterial Properties of Bioplastic
    By hello1019 in forum Biology
    Replies: 2
    Last Post: December 6th, 2013, 02:09 PM
  2. Universe is like a 3D Rainbow (New Proposal)
    By dapifo in forum Personal Theories & Alternative Ideas
    Replies: 116
    Last Post: December 13th, 2012, 02:12 PM
  3. How to write such research proposal?
    By dexoey in forum General Discussion
    Replies: 0
    Last Post: September 9th, 2012, 04:23 PM
  4. Modest Proposal-
    By The Finger Prince in forum Site Feedback
    Replies: 11
    Last Post: November 2nd, 2011, 07:25 PM
  5. Mech Proposal
    By Tharghana in forum Military Technology
    Replies: 12
    Last Post: January 5th, 2009, 06:59 PM
Bookmarks
Bookmarks
Posting Permissions
  • You may not post new threads
  • You may not post replies
  • You may not post attachments
  • You may not edit your posts
  •