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The quest to develop antibacterial and antibiotic substances has often been described as an arms-race, as bacterial life develops resistance, requiring us to develop novel agents which can effectively kill said microbes.

My question is: is it at all possible for a single microorganism to develop resistance to everything we can possibly develop?

There is only so much information-capacity in microorganism DNA to encode the means of resistance to various substances. If we climb the arms-race ladder high enough would a highly-advanced bacteria somehow "forget" how to defend against penicillin, for example?

...or are we utterly boned?

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    $\begingroup$ If there is no advantage for a MO to be resistant to a certain antibiotic, it will very likely loose the resistance over time. Problem is we need to collectively not only stop using penicillin, but likely the whole class of penicillin-derived antibiotics for that to happen. No easy task. $\endgroup$
    – AliceD
    Dec 8, 2015 at 10:49
  • $\begingroup$ When you look at individual bacteria, they would forget how to defend against particular types of antibiotics. Growing in the absence of penicillin, most of them would throw away the resistant genes. The problem is that even very small population among them still carries the resistant genes and they would become dominant when they met penicillin. $\endgroup$
    – 243
    Dec 8, 2015 at 15:58

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This is a theoretical question, which I can't answer, because genetics is not my favorite topic. In practice we only have about a dozen antibiotic classes. There are already panresistant bacterias, which are resistant (as far as I know) all of these classes of antibiotics, so we have already lost.

The causes of our defeat is more interesting I think:

  • Pharmaceutical industry does not have enough interest in the antibiotics research, since it is not as profitable as for example cholesterol reducers. Antibiotics are cheap, and you usually heal after the first treatment, while the research and the clinical trials are really expensive, it is hard to find working chemicals, which do not have severe side effects.

    “We need to shift from the concept of the pharmacy as a ‘shop’ and build a culture of pharmaceutical services. This is already happening in some countries, but we need to make it the rule everywhere,” says Zsuzsanna Jakab, WHO Reg ional Director for Europe. “As pharmacists dispense medicines to patients,they are important allies in our fight against antibiotic resistance. As such, they need to be ena bled to deliver accurate information and counselling on proper antibiotic use.”

    Over 40% of antibiotic prescriptions are inappropri ate, recent studies found. This relates especiallyto antibiotics prescribed for the common cold and sore throat; these most oftenresult from viral infections,on which antibiotics have no effect. Further, in some countries, there is atendency towards self-medication. Inappropriate an tibiotic use is the major driver of growing antibiotic resistance.

    Pharmacists have decisive role in combating antibiotic resistance, says new WHO European survey

  • People with Mycobacter infections does not always do the treatment long enough, so Mycobacters can become resistant to antibiotics.

    Most people with TB are cured by a strictly followed, six-month drug regimen that is provided to patients with support and supervision. Inappropriate or incorrect use of antimicrobial drugs, or use of ineffective formulations of drugs (e.g. use of single drugs, poor quality medicines or bad storage conditions), and premature treatment interruption can cause drug resistance, which can then be transmitted, especially in crowded settings such as prisons and hospitals.

    http://www.who.int/features/qa/79/en/

  • There is no global regulation of how to use antibiotics, so in some countries you can buy them without consulting a doctor and get a prescription. On top of this you can buy antibiotics without prescription on the internet if you want. This leads to overuse of antibiotics, and overusage leads to resistance.

    Self-medication is more common in developing countries due to factors such as ready availability of antibiotics without prescription, the unrestricted access to antibiotics,lack of regulation over drugs, and physicians and pharmacists prescribing and dispensing antibiotics without regard to the cause of infection

    http://article.sapub.org/10.5923.j.cmd.20110101.02.html#Sec3.3.4

    We found 138 unique vendors selling antibiotics without a prescription. Of those vendors, 36.2% sold antibiotics without a prescription, and 63.8% provided an online prescription. Penicillins were available on 94.2% of the sites, macrolides on 96.4%, fluoroquinolones on 61.6%, and cephalosporins on 56.5%. Nearly all, 98.6%, ship to the United States.

    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2746509/

    These results demonstrate that, although illegal, the sale of antibiotics without a prescription continues in Spain.

    http://cid.oxfordjournals.org/content/48/10/1345.full

  • Some of the antibiocstics are used by agriculture industry, which leads to antibiotics resistance as well.

    They identified bacteria able to shrug off the drug of last resort - colistin - in patients and livestock in China.

    It is likely resistance emerged after colistin was overused in farm animals.

    http://www.bbc.com/news/health-34857015

    Nutritive and therapeutic treatment of farm animals with antibiotics, amounting to half of the world's antibiotic output, has selected for resistant bacteria that may contaminate the food produced. Antibiotic-resistant enterococci and staphylococci from animals are found in food when they survive the production processes, as in raw cured sausages and raw milk cheeses1. The broad host ranges of some plasmids and the action of transposons in many bacteria allow antibiotic-resistance genes to be communicated by conjugation between different species and genera2,3. A multi-antibiotic resistance plasmid from a lactococcus found in cheese provides a historical record of such events.

    http://www.nature.com/nature/journal/v389/n6653/abs/389801b0.html

    About 2/3 of the antibiotics are used in animals.

    https://youtu.be/iLJAleLjJv8?t=3m47s

So the problem is with not enough motivation in development and the lack of proper regulation of usage. Regulation is the business of the politicians, so its their fault as always. :D

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  • $\begingroup$ A lot of theorizing about motivation makes for conspiracy-theory-like thinking (Big Pharma, etc.) Some sources to back this up might be nice. $\endgroup$ Dec 8, 2015 at 20:20
  • $\begingroup$ @anongoodnurse I did not add the sources, because it is hard to find in the browser history, but if you really need it, I'll update my post. $\endgroup$
    – inf3rno
    Dec 8, 2015 at 22:46
  • $\begingroup$ @anongoodnurse I still cannot find the documentary about the "big pharma" I wanted to link. :S According to some comments I watched it in march 2015. $\endgroup$
    – inf3rno
    Dec 9, 2015 at 0:03
  • $\begingroup$ I think this is a better answer now; had already upvoted, so can't do so again. I know documentaries can be pretty convincing, but they are not always truthful (honest.) I saw one on a cardiology issue which was so convincing that had I not known for a fact that it was false, I would have had serious doubts about my profession. As it is, I don't know why the makers haven't been sued, but ? $\endgroup$ Dec 9, 2015 at 0:09
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    $\begingroup$ I can't really give hope because a video is not a good reference. But towards the end this video claims that bacteria cannot be immune to both both bacteriophages and antibiotics at the same time. So bacteriophages might help us win provided they don't cause some other disease. https://pubmed.ncbi.nlm.nih.gov/24619620/ $\endgroup$
    – Aurelius
    Nov 25, 2023 at 12:47
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My question is: is it at all possible for a single microorganism to develop resistance to everything we can possibly develop?

If you are only discussing antibiotics, the answer is, yes, it's theoretically possible but very highly unlikely, as different classes of bacteria have different characteristics that allow resistance to certain antibiotics to develop.

For example, if a bacteria doesn't have penicillin-binding proteins - allowing cross-linking and stabilization of the bacterial cell wall - then resistance to this antibiotic which makes susceptible bacteria unable to synthesize their cell walls - is meaningless, so unlikely to happen (except through sharing of useless genetic material, which does have limiting factors.)

If you're discussing all antimicrobials (and you consider something like bleach an antimicrobial), the answer is "no".

The danger isn't that a microbe will be resistant to every antibiotic. The danger is that it will be resistant to enough of them to cause a significant problem. It takes time to test for antibiotic sensitivity; in the meantime, a person with an infection that needs antibiotic treatment is getting sicker. Labs start testing for antibiotic sensitivity with antibiotics that the identified organism is usually sensitive to. If that fails to reveal sensitivity to an antibiotic at acceptable levels - one option is to increase the amount of antibiotic given - new tests need to be carried out, taking even more time (for antibiotic combinations or "atypical" antibiotics). It's possible that an antibiotic (or combination) will be ascertained only after that person's death.

Staph aureus has lived closely with man for I don't know how many hundreds of thousands of years. Most of the time, it's presence is benign. It's only when it becomes invasive that antibacterial resistance is a factor in dealing with it.

Antimicrobial Resistance Learning Site Although this is a veterinary site, it's clear and informative, and, though most people are unaware, use of antibiotics in feed animals - which falls under veterinary medicine - is a major contributor to development and spread of antibiotic resistance.

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A 100% antibacterial resistance is a very dangerous situation, which would mean that the age of antibiotics will be over. To achieve a total resistance the microorganisms would have developed new ways of mutation, transferring genes between them, rapid cell damage repair. It would mark a new step in the evolutionary process. There has been many questions as to whether the age of antibiotics have come to its end or not, but the demand has never been this high. its a very scary scenario, a ticking time bomb.

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    $\begingroup$ The age of antibiotics will never be over. There will be new antibiotics, and there will be fading resistance. But a lot of people will die from once-treatable infections. That's different $\endgroup$ Dec 8, 2015 at 20:29

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