Resisting Resistance
Resisting Resistance
We all know about the antibiotic penicillin. It was discovered in 1927 by Alexander Fleming and since then antibiotics have saved many lives. However, the progress in saving lives that these antibiotics have made is coming to a slowdown due to the fact that relatively recently, microbes have begun to become resistant to antibiotics, they mutate just the tiniest amount and are able to get around the antibiotic and continue to make people sick! This is bad because not only do we have to continuously create new antibiotics, but the microbes are able to develop resistance to even the most powerful antibiotics and we can not make the antibiotics much more powerful or else they will do more harm then good to the person ingesting them. Vancomycin is an antibiotic that doctors are trying to keep as a last resort defense against pathogens. It is worried that bacteria will become resistant to this antibiotic too and then what will we do?
Over 30 years ago it was discovered that deleting certain genes prevents microbes from becoming resistant to antibiotics. Normally, microbes copy their DNA using DNA polymerase (an enzyme) which makes very few mistakes and therefore results in an exact copy of the microbe. No mutations occur and therefore the antibiotic would continue to work on these microbes. However, when a microbe is exposed to antibiotics it becomes “stressed” out and they copy their DNA using normally dormant DNA polymerases that cause many more errors. This is how the microbes mutate; almost by accident! This is quite interesting because it always seemed obvious that the reason these microbes were mutating was because of survival of the fittest. One microbe would mutate and survive and therefore all the microbes would soon be able to resist the drug too.
Hope is near. At the semiannual meeting of the American Chemical Society, researchers from California reported that they have discovered compounds that microbes can not mutate to become resistant too. Although these compounds are not antibiotics, if we could figure out how to do the same thing with antibiotics, or how to make them work alongside antibiotics, the problem of antibiotic resistant microbes would disappear! It may not disappear completely but it could drastically slow down the rate at which microbes mutate which would do us a lot of good. It is a very good thing that scientists are looking into ways to prevent resistance to begin with and are not just continually making new drugs. The better solution would be to figure out a way to keep the microbes from resisting rather than making new drugs everytime they do form resistance.
Floyd Romesberg, a chemist at the Scripps Research Institute in San Diego, California and colleagues decided to look into the phenomenon discovered over 30 years ago. 2 years ago they found that a gene called LexA is an important “on” switch for the DNA polymerase that causes error. They proved this via both in vitro and animal studies. Specifically, they looked for small, drug like molecules that inhibit LexA in microbes exposed to the antibiotic ciprofloxacin. Ciprofloxacin also prevents DNA replication. They screened over 100,000 compounds and found several LexA inhibitors that get inside microbial cells easily and stop bacteria from mutating. It is hard to get things inside microbial cells to begin with so this in itself is an accomplishment.
These compounds are not ready for clinical trials yet but a new biotech company called Achaogen has been created by Romesberg in South San Francisco to commercialize the technology. Hopefully this company will produce compounds that can then go into clinical trials! So if you are interested in these antibiotic resistant microbes, head on over to San Francisco and find the answer!
One important thing to note is that individuals too can play a part in preventing antibiotic resistance. They can do this by simply using antibiotics less; only when absolutely necessary. This will decrease the ability of microbes to become resistant since there is nothing for them to become resistant to! This has actually been proven with penicillin. Read this article for more information.
Posted by KMellman
posted by PWH @ 4:35 PM
8 comments
8 Comments:
This is a really interesting post, and well written. I'm taking two classes right now that have brought up the problem with drug resistance. I know that drug resistance to Tuberculosis drugs are a big issue right now, especially in Russia. In my classes, they brought up unsupervised drug use and irregular drug use as factors that have also lead to antibiotic resistance. Perhaps you could have gone into other factors in your blog. Good work!
kinge06
I like your post because it was well written and very concise!
It is interesting how bacteria are becoming more resistant to antibiotics. Similar to what I learned in Biology 101, random mutations in a bacterium's DNA causes resistance to antibiotics. At the same time, it is scary that this is a reality because antibiotics are widely used and the most common way to cure bacterial infections. If this way of treating disease is ineffective in the future, then what will we use?
This constant battle of new drug warfare versus evolving resistance is certainly a frustrating dilemma. It is fantastic that researchers are investigating the mechanisms of this resistance, rather than constantly just inventing new drugs that will eventually become ineffective anyway. However, I think the final solution to this resistance dilemma would be an absolute cure, ie, the production of medicine that would simply eradicate the disease-causing bacteria.
It's extremely interesting that the mechanism of evolving resistance is not merely "survival of the fittest" as we have thought-rather, as you point out, it appears to be "accidental"! I wonder if this discovery will influence the explanation of the theory of evolution.
Posted by J543
Antibiotic resistance is such a huge problem around the world. One of my classes this semester made this topic part of the class. I hope the microbe that they have discovered can be useful to antibiotics. Is there anything that individuals can do to prevent antibiotic resistance? Good job! barkley519
A very interesting article, and as others have said well written. You started with background info, and ease into the subject of the post. This format helped to make the post more engaging, interesting, and readable even by someone who doesn’t know much about biology. I do have a few questions though. Do you know what exactly allowed the LexA inhibitors to get inside the bacterial cells? Also, how is it that the bacteria cells can’t mutate and become resistant to the inhibitor compounds? Are they a necessary part of the cell?
leboeuf6
The fact that the humans don't use their physical attributes to survive is amazing. We now use our brains to find ways to defeat our adversaries such as creating antibiotics to stop microbes from causing problems within our bodies. It makes sense though that bacterias can find ways to keep on surviving due to natural selection. I personally think that it would be difficult to eradicate this microbes, due to the fact that they existed way before other organisms did.
-dan carlo flores
I decided to comment on this post because I am a microbiology major and a lot of my other classes have touched upon this important topic. I think it is amazing what bacteria and other microbes are able to accomplish. It goes to show you that humans really don't control this planet. Microbes have found a way to live everywhere and they also have found ways to beat drugs specifically designed to kill them.
The point that you brought up though is very interesting and I'm interested to see if it will work.
I, as did many others, found this blog to be very interesting and well written. The topic of resistance is one that I have much interest in and exposure to because of my major. I'm glad to see that developments are taking place in order to try to prevent or slow down resistance rather than just viewing it as an imminent occurance that we will have to try to keep ahead of by inventing new products and medicines to combat the mutated bacteria. As a pre-vet student I find resistance to different drugs to be a big issue in the field, and therefore see that maybe this research could not only greatly benefit humans but hopefully animals as well. As a real life instance: One concern with alpacas is meningeal worm infection (a parasite rather than a bacteria). Alpacas are injected with ivermectin, a very potent anti-parasite treatment, once a month in order to prevent infection with the parasite. Preventative measures are taken rather than treatment because, once infected, the prognosis is grim. Many/most alpacas die from it, once symptoms appear it is usually too late to try and treat (there is no way to test for the presence of the parasite other than at necropsy); and the ones that do survive usually suffer ireversable neurological damage. Owners are growing concerned because they know that eventually the parasites that they are working so hard to prevent infecting their animals will most likely become resistant to the drug. I know that this real life instance demonstrates parasite resistance rather than bacterial resistance, but it is still an issue of mutation to resist a prescribed method of treatment/prevention. I wonder if it would be possible to apply the research on bacterial resistance to parasites and if they mutate in similar ways which could possibly be prevented in the future.
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