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  • fud.fighter2 fud.fighter2 Apr 4, 2014 8:11 AM Flag

    The latest evolutionary step in TB therapy

    This is from an article on the Understanding Evolution site a few years ago which explains why Arikace - the first SAFE aminoglycoside therapy for pulmonary infections - is certain to generate a multi-billion dollar revenue stream ...

    [ Around 1.8 billion years ago a major divergence occurred among the single-celled organisms that then made up life on Earth.

    An early bacterium - one which could use oxygen to release energy from sugars - was engulfed by another bacterium. Through the process of endosymbiosis this lineage eventually evolved into the eukaryotes (the diverse group which includes animals and plants) and the engulfed bacterium evolved into a cellular organelle (the mitochondrion, the powerhouse of the cell), while the relatives of the engulfed bacterium remained single-celled and evolved into modern bacteria.

    As these two lineages - the eukaryotes and the bacteria - proceeded along their independent evolutionary paths, each acquired mutations that affected their cellular machinery.

    To understand the action of aminoglycoside antibiotics, the relevant cell part in each lineage is the ribosome, whose job is building proteins based on instructions from the DNA. Though all ribosomes share many basic characteristics, the eukaryotic ribosome is larger than bacterial ribosomes and is shaped somewhat differently. These differences, which began evolving so long ago, are what allow aminoglycosides to be effective antibiotics instead of dangerous toxins.

    Aminoglycosides attach to the part of the bacterial ribosome that decodes messages from the DNA. By blocking protein synthesis, aminoglycosides prevent the bacterium from reproducing and carrying out its basic functions. Luckily for us, our own eukaryotic ribosomes accumulated just enough differences from bacterial ribosomes that aminoglycosides cannot attach to them and block the functioning of our own cells. ]

    contd ...

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    • TB or MDR-TB would be gravy, but we are close to having a potential patient population of 180,000 in US and Europe between CF and NTM. (BTW, I love how all of the company info now puts NTM before CF since the start of this year.) That should be plenty to make the share price take off.

      If we get any progress in TB that will just be gravy. Tanker truck loads of gravy to drown our meat (NTM) and potatoes (CF).

    • TB application would create a $50billion company.

      Sentiment: Buy

    • Second part -

      [ That means aminoglycosides attack bacteria in our bodies but not the ribosomes of our own cells - with one exception. As described earlier, the mitochondria in our cells are descended from free-living bacteria, and it so happens that our mitochondria have their own ribosomes, which, as you would expect, are more similar to bacterial ribosomes than they are to the ribosomes in the rest of our cells. If aminoglycosides reach the mitochondria in our cells, they can prevent the mitochondria from functioning normally because our mitochondria have such a close evolutionary relationship with bacteria.

      One consequence of aminoglycosides' effects on mitochondrial ribosomes seems to be an occasional case of hearing loss. Apparently, in some people (especially those carrying certain mutations in the gene that codes for their mitochondrial ribosomes), the antibiotic's effect on mitochondria in the inner ear causes the death of hair cells that play an important role in detecting sound. While it is not clear exactly how this occurs, it does seem to be a consequence of our mitochondria's evolutionary relationship with bacteria. Fortunately, most people seem to suffer few negative outcomes as a result of taking aminoglycosides.

      Nevertheless, because of this risk (as well as another potential side effect of the drugs, kidney damage) the medical community has been reconsidering how frequently aminoglycosides such as streptomycin should be deployed. Currently, these drugs still play an important role in fighting diseases like tuberculosis and plague (yep, it's still around!) and are an important part of our antibiotic arsenal when fighting pathogens that have evolved resistance to multiple drugs.

      Whatever the final verdict on their use ends up being, we have evolution to thank for both the utility of these drugs and their undesirable side effects. ]

      Beware of attention-seekers trying to impress you with made-up stories about cell walls.

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