Antibiotic Resistance

[madanthonywayne]

MRSA, once a rare infection mainly acquired in a hospital setting, is now out in the general population. It is very difficult to treat because it is resistant to most antibiotics. Nor is MRSA the only such pathogen out there. More and more are evolving resistance to multiple antibiotics.

There has always been something of an arms race between humans trying to kill disease causing microbes and the microbes themselves. Up to now, we've always been bailed out by the development of new antibiotics. However, pharmaceutical companies have lost interest in developing new antibiotics. Why? To quote a Pharmaceutical executive,

"You take an antibiotic for 2 weeks, and you take a statin the rest of your life. What would you make?​

To illustrate the decline in new antibiotics, consider the fact that from 1983-1987 16 new antibiotics were approved by the FDA; but from 2008-2011 that number was only 2.

Furthermore, As recently as 1990 we had 19 companies developing antibiotics, that number has now declined to 4.

There are some acts before congress that are intended to address this issue such as the GAIN bill in the house and the STAAR bill in the senate).

Of course, these bills have yet to be passed and even if they are successful, we are likely to be dealing with an increasing number of superbugs for the foreseeable future.

http://www.medscape.com/viewarticle/751959?src=mp&spon=17

 

[chimpkin]

Something I was not aware of until I slogged through college biology...horizontal gene transfer.
http://www.sci.sdsu.edu/~smaloy/MicrobialGenetics/topics/genetic-exchange/exchange/exchange.html
So once one bacterium develops resistance, it has non-reproductive ways of passing the resistance around.
Isn't that a happy thought?

 

[Repo Man]

Let's hear it for antibiotic laced animal feed!

 

[Hercules Rockefeller]

AFAIK, antibiotic development to date has revolved around creating compounds that directly kill bacteria (bacteriocidal drugs) or prevent their division (bacteriostatic drugs). However, bacteria are winning this ‘arms race’ so it seems to me that a different approach is needed for future antibiotic development. I like the idea of 'quorum sensing inhibitors' as antibiotic drugs. These compounds do not kill bacteria, rather they inhibit their ability to communicate with each other. When they cannot communicate they cannot form biofilms or coordinate the necessary gene expression for pathogenesis.

The advantage of the anti-quorum sensing approach to controlling infection is that there are few evolutionary forces that select for resistance—there is little in the process that would create resistant strains. Since the compounds kill none of the bacteria, any resistant mutations must compete with living, non-resistant individuals. In other words, there is no survival advantage to the resistant mutations, and natural selection does not come into play. Resistant strains will be unlikely to occur.

http://en.wikipedia.org/wiki/Quorum_sensing

 

[Pineal]

Let's hear it for antibiotic laced animal feed!

And anti-bacterial plastics in children's toys!

 

[Pineal]

Mammals are, yes, a kind of animal. And humans are mammals.

 

[Pineal]

And then there is the use of antiobiotic resistence genes in genetically modified foods. Even some industry reps are concerned about this....

http://www.novozymes.com/en/about-us/positions/Pages/Antibiotic-resistance-genes-in-GMMs.aspx

 

[chimpkin]

hercules Rockefeller:
I like the idea of 'quorum sensing inhibitors' as antibiotic drugs.

So do I...chronic sinus disease is probably biofilm-based, that why antibiotics don't clear it...Mine is still there after two surgeries. Reminds me, I should try irrigating with xylitol again, that seemed to help, but I ran out...

 

[arauca]

calls for antibiotic replacement

(Medical Xpress) -- Most everyone that has been keeping abreast of world events knows that the clock is ticking on antibiotics; bacteria have been slowly developing a resistance and development of new antibiotics has slowed to a crawl, thus the day will soon come that all of the tools were are currently using to fight bacterial infections will be lost, leaving everyone at their mercy. This problem has not gone unnoticed by those at the upper reaches of the military establishment in the United States, thus it should not come as a surprise to anyone that DARPA, via the Small Business Innovation Research (SBIR) program, has issued a Request for Proposals (RFP) to completely replace antibiotics with something new and better.

As noted in the RFP, the military has seen firsthand the problems with current antibiotics; soldiers experiencing wounds in war, especially those involved in fires, that develop bacterial infections now require triple the amount of hospital time to recover as doctor’s plow through a host of antibiotics in trying to find the one that will work. Clearly frightened at the prospect of sending soldiers into battle where they may encounter bioengineered bacterial agents, the top brass has decided it’s time to take another approach and to get on it now.

Instead of working to develop new antibiotics, DARPA proposes the development and use of so-called nanoparticles to deliver gene altering chemicals directly to the cells of bacteria to kill them. In addition, they are hoping that someone will be able to come up with a way to make it so that the nanoparticles and chemicals they carry can be reprogrammed on-the-fly so as to combat newly evolved or created bacteria as soon as they appear. The idea is that the nanoparticles would carry something called small interfering RNA (siRNA) which are groups of molecules that would actually do the work of shutting down the genes inside the cells of the bacteria.

DARPA has laid out the project in three phases: Study what’s out there now, develop the nanoparticle delivery system and siRNA, and devise a means for rapidly reprogramming them.

On its face, the project seems rather simple, after all, this is not science fiction, DARPA points out that just last year a research group used siRNA delivered by nanoparticles to kill the Ebola virus in four primates. Unfortunately, the problem is, it’s not as easy as it looks, all of this science is still in its infancy and if a way can be found to do what is being asked, it likely will take years, if not decades to fully develop. The success against the Ebola virus was one agent against just one virus in a structured environment. To do what DARPA wants would mean using one technique to kill any and all bad bacteria and/or viruses. Also, if it can be done, no one really knows if the procedure would be reprogrammable, much less whether it could be done on-the-fly, so it’s not really clear if anyone will be able to achieve what DARPA is asking for; though it seems for the sake of all of us, we better hope so. Turning back the clock to a time when we were helpless against the onslaught of bacterial infections would be difficult to swallow, to say the least.
http://medicalxpress.com/news/2011-11-darpa-antibiotic.html

 

[Hercules Rockefeller]

I use siRNA in my research. It’s a great tool for basic biology research in cell cultures. I’m pretty sure it has also been extended into a small number of human gene therapy clinical trials to correct genetic defects. However, it’s such a fiddly technology with so many potential variables that there is no way it could be developed as a general replacement technology for antibiotics any time soon.

 

[Cifo]

May 31, 2011 – Excelimmune, Inc. today announced the final closing of a $10.5 million Series B financing. Proceeds from the Series B will enable Excelimmune to advance Staphguard, a human recombinant polyclonal antibody (HRPA) candidate against methicillin-resistant Staphylococcus aureus (MRSA), toward the clinic, enhance the Company’s discovery platform and complete proof-of-principle for its manufacturing systems. The Series B funding was provided by a syndicate of new and existing high net worth individual investors.

source

 

[Walter L. Wagner]

source

Their new product 'Staphgard' sounds interesting. Does it work? Any animal or human tests underway?

 

[Hercules Rockefeller]

It looks like they have secured the funding to start some human clinical trials.

 

[wellwisher]

This is where knowledge of configurational potential and free energy comes in handy. The situation needs logic not random trials. The ability of bacteria to adapt and evolve countermeasures to even artificial/unnatural chemicals produced by humans, it done via free energy in the context of the DNA. Throwing the dice randomly is too slow, so the bacteria make use of free energy to load the dice to get better odds.

 

[Arioch]

@wellwisher --

I don't think that evolution works the way you think it does. The dice are indeed random, but there's also a selection going on which isn't random. It also helps that there are millions or billions of dice in each body(depending on the severity of the infection) and that the dice are being rolled so frequently(bacteria reproduce at a truly frightening pace). All it takes is a couple thousand of those developing the right resistance and the genes for that will spread as the rest are killed by the antibiotics.

When you're dealing with numbers on this scale you don't need weighted dice, purely random dice throwing is more than enough to produce the efficacious mutation and then the nonrandom selection takes over. Come on man, this is basic biology here.

 

[wellwisher]

Basic biology is wrong. If change on the DNA was random, why do certain parts of the DNA change faster than others? That does not make logical sense. This is like throwing a dice and 1 and 2 appearing more than 3,4,5,6 most of the time. Basic biology assumes loaded dice are legitimate dice. That is cheating. The cheating got science so far but now the bacteria are ahead.

Maybe we can prove this with a computer simulation. We can use the DNA from a bacteria. We will also use the random mutation assumption. That means each base pair will have equal likelihood of mutating at the same rate; This is like the six sides of the dice each coming up 1/6 over time. If we have 10,000,000 base pairs, that means each base pair will have programmed odds of 1/10,000,000. Then we will see how it evolves. It will not work. This is not cheating.

To get it to evolve we need to load the dice using free energy. Does anyone have the computer skill to do this so we can settle this once and for all?

 

[spidergoat]

There is a degree of redundancy in certain essential aspects of the genome.

 

[Arioch]

@wellwisher --

why do certain parts of the DNA change faster than others? That does not make logical sense.

While not wishing to insult your obviously superior knowledge of biology, this isn't some conundrum that has biologists everywhere baffled, in fact we've known why different bits of DNA change at different rates for quite a while now(Dawkins wrote about it over thirty years ago).

You see, not all of the different bits of DNA are subject to the same degree of selection, some are selected for heavily and some(the ones that don't code for a protein) are subject to very little selection at all. DNA for growing functioning lungs(or gills, take your pick) is obviously going to be subject to intense selection and thus won't change as much or as fast. Random changes are most likely going to be in the "less functional" direction and "less functional" lungs are something that natural selection just won't tolerate(because the given individual will be less fit) and thus such genes won't vary too much too frequently. DNA that either doesn't code for anything or codes for something that is useful but not necessary(such as the difference between being a dichromat or a trichromat) isn't going to be subject to such stringent and will therefore be free to change quite a bit and more frequently.

No, evolutionary theory accounts for this phenomenon quite nicely. You, just like a creationist, are leaving out the nonrandom selection part of evolution and focusing exclusively on the random mutation part of it.

This is like throwing a dice and 1 and 2 appearing more than 3,4,5,6 most of the time.

No, it's like throwing dice again and again while holding the ones you want to keep. If you're going to try to explain things metaphorically then you could at least try to get the metaphor right.

Basic biology assumes loaded dice are legitimate dice.

Nope, basic biology "assumes" a selection factor because one is evident. Even random dice throws will give you what you want if you have enough dice and you can keep the ones you want, all you have to do is keep throwing and you'll get there eventually.

Then we will see how it evolves. It will not work. This is not cheating.

Alright, but with one added feature to make it match nature somewhat better, we get to keep the genes we want from every generation. We'd still see evolution, but at a much slower rate because you are ignoring the fact that not all genes face the same selection pressure.

To get it to evolve we need to load the dice using free energy. Does anyone have the computer skill to do this so we can settle this once and for all?

Do you have any idea how many "evolution" programs are out there? I have two on my computer right now, all of them replicating nature much better than yours would(which means that they're closer to reality than yours would be).

I honestly don't expect you to even attempt to follow up on this by researching what evolutionary theory actually says opposed to your twisted straw man version of it. You and the IDiots have a lot in common.

 

[Aqueous Id]

Yes MRSA is a serious consequence of evolution by selection of drug resistant traits. Hopefully this new research will break new ground and spare countless lives and injuries. It's a very worthwhile investment. Sources I've read have been long complaining about the gradual ineffectiveness of conventional methods, a dwindling arsenal of useful anti-microbials, and the urgency of finding alternatives.