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I wonder how these bacteria can /remain/ resistant against older antibiotics. If they mutate really fast, should not the resistance against, say penicillin, van

I wonder how these bacteria can /remain/ resistant against older antibiotics. If they mutate really fast, should not the resistance against, say penicillin, vanish after a few years when they are not exposed to the medicine? So could we not "renew" some antibiotics by simply not using them for 5 to 10 years?

AstralStorm 8y ago
Depends. The multidrug resistant variants tend to be resistant to most everything and this resistance does not cost them enough for it to get discarded. Moreover certain viruses cause the resistance to spread horizontally, and some bacteria do share genomes locally as well.
alfredallan1 8y ago
It is not necessary that mutation would cause the loss of a previously developed resistance. It is not just the bacteria that grow resistant to drugs, but the human body itself starts to develop resistances. One of the major factors behind this is the presence of antibiotics in the various meats we consume. Animal antibiotics are a huge gift to the factory farming industry. But to acheive better results, many animal farmers simply (and often illegally) use the highest dose of the antibiotic they can find. A small amount of these drugs eventually make their way to human bodies. Persistent exposure to such drugs then results in increased resistance to antibiotics. So where previously a regular dose of a milder antibiotic would have sufficed, now a high dosage of a strong antibiotic is required.
- chiasmic 8y ago
  Could you provide some evidence to back up your statement? As far as I am aware, antibiotics directly impact bacteria via impairing DNA, ribosomal, or cell wall synthesis. The human body does break down antibiotics via the liver, and it’s rate can be increased by numerous drugs (but not normally antibiotics) and this would not be seen as resistance. I don’t think the concept of human resistance to antimicrobrials is consistent with conventional biological knowledge.
  - alfredallan1 8y ago
    If you do a quick google search for “human resistance to antibiotics” you’ll find a number of good results. Any evidence I would cite would be from the more reputable sources, such as government agency websites, wiki, known scientific publications. https://www.google.com/search?rls=en&q=human+resistance+to+antibiotics https://www.google.com/search?rls=en&q=human+resistance+to+a... While I’m not a trained professional in that area to debate the specific mechanisms, I am sufficiently informed from sufficiently reliable sources about the topic. As an example, this report from the US National Institute of Medicine titled “The Antibiotic Resistance Crisis” seems to strengthen the case the article linked by the OP of this thread is making. To quote selectively from the aforementioned report, "The overuse of antibiotics clearly drives the evolution of resistance. Epidemiological studies have demonstrated a direct relationship between antibiotic consumption and the emergence and dissemination of resistant bacteria strains. In bacteria, genes can be inherited from relatives or can be acquired from nonrelatives on mobile genetic elements such as plasmids. This horizontal gene transfer (HGT) can allow antibiotic resistance to be transferred among different species of bacteria. Resistance can also occur spontaneously through mutation. Antibiotics remove drug-sensitive competitors, leaving resistant bacteria behind to reproduce as a result of natural selection. Despite warnings regarding overuse, antibiotics are overprescribed worldwide" “Incorrectly prescribed antibiotics also contribute to the promotion of resistant bacteria” "More recently, molecular detection methods have demonstrated that resistant bacteria in farm animals reach consumers through meat products. This occurs through the following sequence of events: 1) antibiotic use in food-producing animals kills or suppresses susceptible bacteria, allowing antibiotic-resistant bacteria to thrive; 2) resistant bacteria are transmitted to humans through the food supply; 3) these bacteria can cause infections in humans that may lead to adverse health consequences." Should you wish to debate the technicalities of the topic further, I can only suggest waiting for a trained microbiologist to show up in this thread, or getting in touch with the authors of the aforementioned report and the various references linked therein (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4378521/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4378521/)
    - chiasmic 8y ago
      Perhaps I miss understand you more than anything. Thank you for the quotes and papers. I agree with you that antibiotic resistance (of bacteria) can rise due to the use in the harm industry, the part that I am sceptical is your statement that the human body itself becomes resistant to antibiotics. The sources you provided discuss bacterial resistance, which is very different from human body resistance.
jhbadger 8y ago
It depends on how the resistance works. Some forms of resistance require active effort by the bacterium (for example efflux pumps), and you would expect that in the absence of an antibiotic they would tend to be lost by natural selection. But other forms of resistance are just minor mutations stopping the antibiotic from binding or whatever, and these probably would remain at least in some fraction of the bacterial population as they are more or less neutral.
- Retric 8y ago
  The human immune system can deal with a huge range of things just fine. So, the metabolic weight from antibiotic resistance is inherently useful for Humans. Antibiotic resistant bacteria do kill people, but most often as secondary infections due to a compromised immune system. Further, even if the primary infection has near total resistance suppressing secondary infections is still extremely useful.
  - aaron_m04 8y ago
    Are you saying the adaptations bacteria make to become resistant to antibiotics causes them to be easier targets for the immune system? Do you have a link I could read more about this?
    - Retric 8y ago
      Yes, but not always, and not necessarily for long. "While the cost of resistance is highly variable, such resistance mutations or genes often come with a fitness cost that reduces the rate of bacterial proliferation (Dahlberg & Chao, 2003; Melnyk et al, 2015)." https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5371735/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5371735/ "The success of resistant mutants critically depends on rapid counterbalancing of the decreased fitness by acquiring compensatory mutations (Levin et al, 1997; Marciano et al, 2007), which in most cases restore normal growth while preserving resistance to the antibiotics (Marcusson et al, 2009). The number and variety of compensatory mutations required to successfully compensate fitness cost varies with organism (Palmer & Kishony, 2013, 2014; Cheng et al, 2014) and the particular environmental conditions under which compensation occurs (Testerman et al, 2006; Hoffman et al, 2010; Toprak et al, 2012; Lindsey et al, 2013)." Basically, resistance become extremely important so anything that works get's adapted. But, after that point the search for mutations that reduce cost shows up. The second stage also depends on continuous exposure to antibiotics as reverting the mutation in a population is relatively simple.
delibes 8y ago
> So could we not "renew" some antibiotics by simply not using them for 5 to 10 years? I'm fairly sure I've come across this idea before. Oh here's an example: https://www.quora.com/What-is-antibiotic-rotation https://www.quora.com/What-is-antibiotic-rotation Seems like the problem is how long it takes to lose the resistance. Probably a few decades rather than a few years. And you'd need all the world to stop, which just isn't going to happen in Asia, Africa, South America where you can just buy a couple of pills from the local pharmacist if that's all you can afford. Not an easy problem to deal with sadly.
- deleted 8y ago
  [deleted]
criddell 8y ago
You might enjoy this episode of Radiolab: https://www.wnycstudios.org/story/best-medicine/ https://www.wnycstudios.org/story/best-medicine/ They take a thousand year old recipe for some medication and test it.
kurthr 8y ago
Unfortunately, the genes developed for resistance are still present in a certain portion of the pool... so that when antibiotics are used it only takes 1 to multiply exponentially and destroy the resistance. Some of the genes cost little extra to be selected against... and even when an expensive group are selected against, it can split up into more than one survivor and then the combination will be selected for again. Like old code... most of those once useful genes don't ever fully go away.
DamnInteresting 8y ago
I asked something similar in a reddit AMA[1] with Mark Blaskovich, from Open Antimicrobial Drug Discovery. His answer wasn't super satisfying, but for what it's worth: > The resistance genes will likely remain, but be 'switched off', so resistance would re-emerge quickly. The cycling approach could theoretically work to some extent, but the logistics on a worldwide scale would be impractical. Mark B [1] https://www.reddit.com/r/science/comments/3k32wi/american_chemical_society_ama_series_im_mark/cuuedmi/ https://www.reddit.com/r/science/comments/3k32wi/american_ch...

AstralStorm 8y ago

Depends. The multidrug resistant variants tend to be resistant to most everything and this resistance does not cost them enough for it to get discarded. Moreover certain viruses cause the resistance to spread horizontally, and some bacteria do share genomes locally as well.

alfredallan1 8y ago

It is not necessary that mutation would cause the loss of a previously developed resistance. It is not just the bacteria that grow resistant to drugs, but the human body itself starts to develop resistances. One of the major factors behind this is the presence of antibiotics in the various meats we consume. Animal antibiotics are a huge gift to the factory farming industry. But to acheive better results, many animal farmers simply (and often illegally) use the highest dose of the antibiotic they can find. A small amount of these drugs eventually make their way to human bodies. Persistent exposure to such drugs then results in increased resistance to antibiotics. So where previously a regular dose of a milder antibiotic would have sufficed, now a high dosage of a strong antibiotic is required.

chiasmic 8y ago
Could you provide some evidence to back up your statement? As far as I am aware, antibiotics directly impact bacteria via impairing DNA, ribosomal, or cell wall synthesis. The human body does break down antibiotics via the liver, and it’s rate can be increased by numerous drugs (but not normally antibiotics) and this would not be seen as resistance. I don’t think the concept of human resistance to antimicrobrials is consistent with conventional biological knowledge.
- alfredallan1 8y ago
  If you do a quick google search for “human resistance to antibiotics” you’ll find a number of good results. Any evidence I would cite would be from the more reputable sources, such as government agency websites, wiki, known scientific publications. https://www.google.com/search?rls=en&q=human+resistance+to+antibiotics https://www.google.com/search?rls=en&q=human+resistance+to+a... While I’m not a trained professional in that area to debate the specific mechanisms, I am sufficiently informed from sufficiently reliable sources about the topic. As an example, this report from the US National Institute of Medicine titled “The Antibiotic Resistance Crisis” seems to strengthen the case the article linked by the OP of this thread is making. To quote selectively from the aforementioned report, "The overuse of antibiotics clearly drives the evolution of resistance. Epidemiological studies have demonstrated a direct relationship between antibiotic consumption and the emergence and dissemination of resistant bacteria strains. In bacteria, genes can be inherited from relatives or can be acquired from nonrelatives on mobile genetic elements such as plasmids. This horizontal gene transfer (HGT) can allow antibiotic resistance to be transferred among different species of bacteria. Resistance can also occur spontaneously through mutation. Antibiotics remove drug-sensitive competitors, leaving resistant bacteria behind to reproduce as a result of natural selection. Despite warnings regarding overuse, antibiotics are overprescribed worldwide" “Incorrectly prescribed antibiotics also contribute to the promotion of resistant bacteria” "More recently, molecular detection methods have demonstrated that resistant bacteria in farm animals reach consumers through meat products. This occurs through the following sequence of events: 1) antibiotic use in food-producing animals kills or suppresses susceptible bacteria, allowing antibiotic-resistant bacteria to thrive; 2) resistant bacteria are transmitted to humans through the food supply; 3) these bacteria can cause infections in humans that may lead to adverse health consequences." Should you wish to debate the technicalities of the topic further, I can only suggest waiting for a trained microbiologist to show up in this thread, or getting in touch with the authors of the aforementioned report and the various references linked therein (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4378521/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4378521/)
  - chiasmic 8y ago
    Perhaps I miss understand you more than anything. Thank you for the quotes and papers. I agree with you that antibiotic resistance (of bacteria) can rise due to the use in the harm industry, the part that I am sceptical is your statement that the human body itself becomes resistant to antibiotics. The sources you provided discuss bacterial resistance, which is very different from human body resistance.

jhbadger 8y ago

It depends on how the resistance works. Some forms of resistance require active effort by the bacterium (for example efflux pumps), and you would expect that in the absence of an antibiotic they would tend to be lost by natural selection. But other forms of resistance are just minor mutations stopping the antibiotic from binding or whatever, and these probably would remain at least in some fraction of the bacterial population as they are more or less neutral.

Retric 8y ago
The human immune system can deal with a huge range of things just fine. So, the metabolic weight from antibiotic resistance is inherently useful for Humans. Antibiotic resistant bacteria do kill people, but most often as secondary infections due to a compromised immune system. Further, even if the primary infection has near total resistance suppressing secondary infections is still extremely useful.
- aaron_m04 8y ago
  Are you saying the adaptations bacteria make to become resistant to antibiotics causes them to be easier targets for the immune system? Do you have a link I could read more about this?
  - Retric 8y ago
    Yes, but not always, and not necessarily for long. "While the cost of resistance is highly variable, such resistance mutations or genes often come with a fitness cost that reduces the rate of bacterial proliferation (Dahlberg & Chao, 2003; Melnyk et al, 2015)." https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5371735/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5371735/ "The success of resistant mutants critically depends on rapid counterbalancing of the decreased fitness by acquiring compensatory mutations (Levin et al, 1997; Marciano et al, 2007), which in most cases restore normal growth while preserving resistance to the antibiotics (Marcusson et al, 2009). The number and variety of compensatory mutations required to successfully compensate fitness cost varies with organism (Palmer & Kishony, 2013, 2014; Cheng et al, 2014) and the particular environmental conditions under which compensation occurs (Testerman et al, 2006; Hoffman et al, 2010; Toprak et al, 2012; Lindsey et al, 2013)." Basically, resistance become extremely important so anything that works get's adapted. But, after that point the search for mutations that reduce cost shows up. The second stage also depends on continuous exposure to antibiotics as reverting the mutation in a population is relatively simple.

delibes 8y ago

> So could we not "renew" some antibiotics by simply not using them for 5 to 10 years? I'm fairly sure I've come across this idea before. Oh here's an example: https://www.quora.com/What-is-antibiotic-rotation https://www.quora.com/What-is-antibiotic-rotation Seems like the problem is how long it takes to lose the resistance. Probably a few decades rather than a few years. And you'd need all the world to stop, which just isn't going to happen in Asia, Africa, South America where you can just buy a couple of pills from the local pharmacist if that's all you can afford. Not an easy problem to deal with sadly.

deleted 8y ago
[deleted]

criddell 8y ago

You might enjoy this episode of Radiolab: https://www.wnycstudios.org/story/best-medicine/ https://www.wnycstudios.org/story/best-medicine/ They take a thousand year old recipe for some medication and test it.

kurthr 8y ago

Unfortunately, the genes developed for resistance are still present in a certain portion of the pool... so that when antibiotics are used it only takes 1 to multiply exponentially and destroy the resistance. Some of the genes cost little extra to be selected against... and even when an expensive group are selected against, it can split up into more than one survivor and then the combination will be selected for again. Like old code... most of those once useful genes don't ever fully go away.

DamnInteresting 8y ago

I asked something similar in a reddit AMA[1] with Mark Blaskovich, from Open Antimicrobial Drug Discovery. His answer wasn't super satisfying, but for what it's worth: > The resistance genes will likely remain, but be 'switched off', so resistance would re-emerge quickly. The cycling approach could theoretically work to some extent, but the logistics on a worldwide scale would be impractical. Mark B [1] https://www.reddit.com/r/science/comments/3k32wi/american_chemical_society_ama_series_im_mark/cuuedmi/ https://www.reddit.com/r/science/comments/3k32wi/american_ch...