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Author: Subject: Bacterial resistance to antibiotics.
crazyboy
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[*] posted on 29-7-2015 at 18:30


Well this devolved quickly.

There are many mechanisms by which bacteria can become antibiotic resistant but I think the scariest is upregulated efflux pumps which pump out antibiotics with little specificity. There have been investigations into efflux inhibitors but ultimately bacteria can and will become resistant to these if they reach the market.

Personally I don't see this problem going away soon. The solution is not completely straight forward but would certainly involve a dramatic decrease in antibiotic consumption. Drug discovery is too slow and expensive to remain effective in such an unprofitable market. If there is a solution I imagine it will rely on phages, bacterial analogs of siRNA, or CRISPR interference because those platforms could easily be modified to different targets across species and rely on DNA or RNA synthesis rather than organic chemistry. Of course just as bacteria have developed nonspecific resistance to many classes of antibiotics it is not unforeseeable that they could develop nonspecific resistances to these new treatments.

Perhaps refraining from using certain classes of antibiotics globally could reduce selection pressure for resistance to that particular antibiotic and we could cycle in this way repeatedly. Probably not feasible due to the limited classes and the necessity for as wide a range as possible especially in the areas with high rates of multiple resistant strains such as hospitals.



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ziqquratu
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[*] posted on 29-7-2015 at 19:06


Quote: Originally posted by crazyboy  
Well this devolved quickly.


Seems to be happening a lot lately... maybe I'm just paying more attention to it, though.

I tend to agree - traditional antibiotics will retain their place as a mainstay of therapy, but new mechanisms based around phages, for example, will have to be developed to treat highly resistant infections. Phages, in particular, have the advantage that the virus should, or average, evolve faster than the bacteria (due to shorter generation time and larger copy number), so development of resistance should be very slow.

Quote: Originally posted by crazyboy  

Perhaps refraining from using certain classes of antibiotics globally could reduce selection pressure for resistance to that particular antibiotic and we could cycle in this way repeatedly. Probably not feasible due to the limited classes and the necessity for as wide a range as possible especially in the areas with high rates of multiple resistant strains such as hospitals.


The problems with that are many, unfortunately. In addition to the considerations you've outlined, antibiotic resistance will (probably) never disappear simply because the selection pressure does - the genes for most resistance mechanisms can simply be turned off, and thus cost the organism almost nothing in terms of fitness, but remaining in the gene pool should the selection pressure return. In addition, many mechanisms target multiple classes of antibiotics - efflux pumps, which you identified, being a major example of this - so sequestering some drugs would have no effect on that type of resistance.

The solution to the problem is complex and requires multiple approaches. New drugs would certainly be welcome, and whole new types of therapy (phages etc.) will also likely be required. Improved prescribing and patient compliance (which requires education of doctors and patients) are critical, as is elimination of antibiotic misuse in the agricultural sector. This is also an area where your suggestion to reserve particular antibiotics could work - we can make sure that animals never receive certain antibiotics (or even classes of them), thus reserving those drugs for human infections and, hopefully, slowing the development and spread of resistance.

The development of better diagnostic tools (which would allow for better prescribing choices), and research to enable more effective use of antibiotics (for example, what dose is effective and how long should treatment go on for) or to improve decisions about whether antibiotics are required at all (for example, I understand that there's mounting evidence against the need for or effectiveness of antibiotic prophylaxis prior to many types of surgery) are all going to be important, too.
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franklyn
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[*] posted on 4-8-2015 at 12:30


The alternative , Phages are natually occuring agents and so do not require the same testing as drugs.
Since western medicine is wedded to pharmaceutical usage this treatment is uninvestigated.

http://en.wikipedia.org/wiki/Phage_therapy
http://www.nature.com/news/phage-therapy-gets-revitalized-1....
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC90351
http://www.themadscienceblog.com/2013/09/phage-therapy-old-i...
http://bullshitcitynorth.blogspot.com/2010/12/phage-therapy-...



Quote: Originally posted by aga  
To be fair, the human population is out of control.


Oh my , aga , incredibly this myth persists.

http://www.sciencemadness.org/talk/viewthread.php?tid=6372&a...

Bangladesh has a greater population at 158 million than Russia with 142 million.
in a country just 1/118 the size , 144000 sq km to Russia's 17 million sq km.
an area smaller than the state of Iowa. Yet the fertility of the Ganges delta assures
agricultural bounty. By example Bangladesh shows that scenarios of overpopulation
bringing biblical ruin to world civilization is all fanciful imagery. In the parlance of
environmentalists it is ' sustainable '.

http://www.youtube.com/watch?v=QwfH1gYkXTw
http://www.census.gov/newsroom/releases/img/babyboomers_pyra...
http://www.youtube.com/watch?v=XNxAzHSprug&t=28m56s
http://www.youtube.com/watch?v=L8XQjfG2wYc


A side note : The central premise of anthropomorphic climate change is that people are the cause.
Assuming for argument that this could be true , it will never happen because the people are not
going to be here to make it happen.




Techniques to Disrupt, Deviate and Seize Control of an Internet Forum In case you wonder W T F ! is going on here ?
www.zerohedge.com/contributed/2012-10-28/cointelpro-techniques-dilution-misdirection-and-control-internet-forum https://web.archive.org/web/20120814124000/www.washingtonsblog.com/2012/08/the-15-rules-of-internet-disinformation.html
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crazyboy
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[*] posted on 4-8-2015 at 14:05


franklyn, I think the argument that overpopulation is a nonissue because India has over 1 billion people and can feed itself is spurious. India is a developing nation and many of its inhabitants live in extreme poverty, as India becomes richer it will consume vastly more resources including electricity, petroleum, water, and consumer goods. As nations develop they inevitably consume more fish, meat, and milk all of require more water and energy to produce than the equivalent calories in plants. The US comprises 5% of the global population but consumes 24% of global energy, imagine the resources needed such that the rest of the world could enjoy the energy consumption of the US.

That said I'm not a population freak, I believe most projected estimates have global population stabilizing around 9 billion in 2050 as fertility rates continue to trend downward as nations develop. While I'm not particularly concerned about our ability to feed ourselves I do think that climate change is a serious issue that will likely remain largely unresolved. When the ozone was being destroyed it was relatively easy to curb the use of CFCs, the same is not true of carbon emissions. I suspect any cuts to global carbon emissions will be largely symbolic and by the time nations are seriously ready to address climate change it will be too late in some respects.

Back to the topic at hand though, one reason I am optimistic about the potential of phage therapy despite it's lack of attention in the west is the increasingly lower cost of DNA sequencing and synthesis. In the near future these technologies will be significantly affordable such that pathogenic bacteria presenting in infections can be rapidly sequenced and a DNA or RNA sequence for a phage which attacks that species or strain of bacteria could be synthesized on site. JCVI is working on such a technology for rapid vaccine development which could be applicable: http://www.jcvi.org/cms/press/press-releases/full-text/artic...

This could be used to build libraries of phages, and new phages would be produced when a new strain emerges. Although bacteria would evolve resistance the ubiquity of phages in the natural world indicates that an evolutionary arms race is sustainable and possibly winnable.
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ziqquratu
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[*] posted on 4-8-2015 at 16:24


Quote: Originally posted by franklyn  
The alternative , Phages are natually occuring agents and so do not require the same testing as drugs.
Since western medicine is wedded to pharmaceutical usage this treatment is uninvestigated.
[/font]


Morphine is a naturally occurring agent, and yet it seems to make drug manufacturers a significant amount of money. Last I checked, aspirin continues to sell rather well. Just about all of the traditional antibiotics - and many of the modern ones - are entirely derived from natural sources (usually by fermentation using appropriate yeasts/fungi). And you can get your lovastatin from red yeast rice or from Merck - the choice largely depends on how you feel about quality control.

Last I heard, around half of all drugs currently on the market are either natural products or directly derived from natural products. And these drugs can all be patented and profitable - even without patents they can be very profitable (morphine!).

Likewise, many phage therapies would be readily patentable, and would be evaluated and regulated just like any other pharmaceutical. One of the major problems facing phage therapy, as far as evaluating safety and efficacy, is that consistency between batches is very difficult to achieve - due to the high mutation rate, what goes in to a production vessel (or a patient!) is likely to be quite different to what comes out! This might require regulatory agencies to consider them slightly differently to a traditional small molecule drug, but that process is already becoming more common due to the emergence of so-called "biologics" which have related difficulties.

In contrast to your claims, phage therapy has been very broadly investigated. The review article you provided from 2001 (14 years ago!) gives a mere 78 references (although it clearly states that it's not trying to be comprehensive). In contrast, a quick PubMed search for "phage therapy" returns nearly 18,000 hits! Hardly what I'd call "uninvestigated". If you read the article you provided, you'll see that it actually discusses why phage therapy isn't in widespread use - primarily lack of reliable data, poor efficacy and difficulties in preparation and administration.

I note the nature article you provided talks about problems with patentability of phage therapy, which, if true, would support your "no profit" argument. Of course, if we observe that:
  • that type of Nature article is written by a journalist, not a practising lawyer, and thus lacks reliability on the point;
  • there is well established precedent regarding the patentability of isolated natural products for therapeutic uses;
  • you can usually patent processes even if "composition of matter" cannot be patented in a particular case;
  • engineered phages - either through molecular methods or via something akin to "selective breeding" - are almost certainly more likely to be better "drugs" than the naturally available options, and are inherently more patentable

we might conclude that patentability isn't too much of a problem.


To population - I recall hearing about a (recent?) "analysis" which claimed that the entire 7 billion people on the planet could comfortably fit into Texas (with space equivalent to a typical New York apartment or something). That might well be true. But it's not all about living space. We each use a LOT of land, much of which we will never set foot on. We need land to grow food (and, coincidentally, we tend to like to live in the areas which would be optimal for food growth, since the climate is so nice, there's plenty of water and just the right amount of sun, which means food production often takes place in less optimal locations). Oh, and don't forget about water! We need a lot of that, and it needs to be stored somewhere in between "delivery" and use! And, of course, we need space to park our cars, moor our yachts, hunt with our weapons, school our children, warehouse goods prior to sale - heck, to house our home chemistry labs! And we also have to leave a little space for the other species on the planet...

Aside from food production, however, we also need resources - all of which are, to one degree or another, limited. Plants tend to like a bit of soluble nitrogen and phosphorous in their diet, which is depleted when the plants are removed so that we can turn them into food (and our efforts to recover trace nutrients from waste streams are woeful - it's cheaper to produce more ammonia or mine more phosphates and ship them in). We require half the periodic table just to get our computers running so that we can have these discussions - and many of those elements are difficult to come by. We need lots of energy - and thus lots of coal, oil, gas, uranium and, indeed, space to house power plants, mines, solar arrays and wind farms!

Please, at least be better than to equate "overpopulation" with "running out of space." I doubt that anyone who makes claims about overpopulation really thinks that "space" is the problem.
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