I've heard for years that low-level use of antibiotics causes the spread of drug-resistant strains of bacteria, but the explanations always fall short. I understand mutations and natural selection, and that a bacterium can randomly mutate into one that is more resistant to the antibiotic than the wild-type. I understand that the antibiotics kill off the less resistant strains and leave the more resistant ones, but those more resistant strains would be there even without the antibiotic use, right?

Do the more resistant bacteria compete somehow with the less resistant ones and the antibiotics kill off the competition?

(Edited: previously used the terms "strong" and "weak" which apparently have unintended connotations, and was unclear about the role of mutation).

  • 1
    $\begingroup$ The last part of your question is confusing. Can you reword your question and talk about mutants and wild-type instead of "strong" and "weak"? Those are value-laden words, and may not even apply to the populations you're talking about. $\endgroup$
    – MattDMo
    Oct 11, 2015 at 3:03
  • $\begingroup$ Resistance to an antibiotic doesn't make it "strong"; it makes it resistant to an antibiotic. If it happens to take hold in a wound, it will flourish no better than a wild-type bacteria, but it will survive exposure to the antibiotic, that's all. $\endgroup$ Oct 11, 2015 at 3:33
  • $\begingroup$ Resistant strains might have been there but they would not have been in a position to outcompete the nonresistants without selection, for the reasons I gave in my answer. If you properly treat bacterial infections long enough and at a high enough dose with a combination of drugs, and have a patient with a functioning immune system, then the adaptive immune response should be able to clear the infection. When we didn't allow that to happen, or we gave antibiotics for viruses, we selected for the resistant mutants, and the adaptive response wasn't able to target and clear them. $\endgroup$
    – AMR
    Oct 12, 2015 at 21:37

2 Answers 2


There is no such thing as a "stronger" or "weaker" strain until the bacteria are treated with antibiotics.

It is true that potentially antibiotic-resistant mutants will still occur whether or not treated with antibiotics.

However, the mutants would not be "stronger" without the antibiotic use, so there is no selective pressure for them to survive to any greater degree than the wild-type. Without the antibiotic, something else will kill that mutant bacteria, meaning that the mutation ultimately did not make it any stronger.


All things being equal, in an environment without the selective pressure of the antibiotic, then the non-resistant wild-type will have a growth advantage.


The events of random mutation and the attendant natural selection in the presence of a given antibiotic provide ample opportunity for the advent of the resistance phenotype. It is interesting to note that the survival cost to the microorganism in the evolution of drug resistance is high as it is highly dependent on the environment in which it happens to exist momentarily. One could envision that in the case of a plasmid-borne resistance factor, the organism must synthesise the additional genetic material and the protein that it encodes. However, this energy cost factor may be affected by the nutritional limits of the environment in which the organism finds itself. Furthermore, alterations of chromosomal genes encoding the targets for antibacterials may present the opportunity for the selection of resistance to antibiotics. However, such modifications may jeopardise the normal function of the gene products and make the organism that carries them less fit in the wild, or diminish or lose the capacity to survive in the absence of the antibiotic. Numerous studies indicate that genetic adaptation by secondary mutations elsewhere in the genome and natural selection reduces this ‘cost’ to the organism in several generations of growth, such that the cost is either reduced or eliminated entirely. Indeed, recent studies suggest that a progression of bacterial resistance to given noxious agents involves a sequence mechanism that renders the organism increasingly resistant to the agent, but nevertheless at a cost to its survival fitness

-Martins, A., Spengler, G., Molnár, J. and Amaral, L. 2014. Bacterial Antibiotic Resistance. eLS.

In order to truly grant resistance to an antibiotic, the bacterium needs to be expressing the enzyme the confers resistance constitutively so that it can react to the antibiotic when the cell comes in contact with the antibiotic. If the bacterium has to wait until it encounters the antibiotic to start expressing the resistance gene, then the bacterium will likely be killed before it has a chance to produce the protein that will protect it. This is especially true for antibiotics that target the bacterial ribosomes to prevent protein synthesis.

The result is that the bacterium has to use energy to produce the enzyme. It also has to maintain that gene either on a plasmid or incorporated in a very small genome. That again means the resistant cell needs more energy for replication, and likely a bit more time to divide. That may seem trivial, but if the nonresistants can divide every 20 minutes while it might take the resistants 25 or 30 minutes, the resistant bacteria will be out competed by the nonresistant bacteria, for the simple fact that the nonresistants are using less energy to survive and replicate and they are doing it faster, so the will have more descendants.

Another thing that you need to realize is that a lot of times the use of antibiotics only holds a bacterial infection in check until our adaptive immune system can be raised and respond to the infection. So not completing a course of antibiotics means that during the period of time that the antibiotic was used the resistant bacteria had a growth advantage over the nonresistant bacteria.

If you stop taking the antibiotic before the immune system can clear the infection completely, then both types of bacteria will begin to divide again, and there will be more of the resistant bacteria than there will be nonresistant, so they will contribute more descendants to the reemerging infection.

Another problem is that the more resistant bacteria there are the more of a chance there is that they can pass on that resistance gene to bacteria that didn't have it before. Now when you go back on the antibiotic, less and less of the bacteria in the infection will be affected, and you will get uncontrolled growth of the infection. There is a point where your immune system either is overwhelmed and cannot respond, the toxicity level from endo and exo toxins produced by the bacteria makes you very sick, or your immune response responds too strongly and does significant damage to your own tissue trying to fight off the bacteria.

  • $\begingroup$ "All things being equal, in an environment without the selective pressure of the antibiotic, then the non-resistant wild-type will have a growth advantage." Do you have a source for this? CA (community associated)-MRSA has mostly replaced HA (hospital associated)-MSRA because their doubling time is much less, giving them a competitive advantage over even "feral" SA unrelated to their methicillin resistance. $\endgroup$ Oct 12, 2015 at 6:12
  • $\begingroup$ @anongoodnurse Your example is of an already resistant, already highly virulent strain of bacteria, and that is not what I am describing. I am describing how you go from a situation where the majority of the organisms are non-resistant and then through the incorrect use of antibiotics, you give rise to strains that have resistance. $\endgroup$
    – AMR
    Oct 12, 2015 at 7:19
  • $\begingroup$ Must it be incorrect use? What about correct use? All I'm asking for is a source to back up your claims. If you don't have one (or more), it's just opinion. $\endgroup$ Oct 12, 2015 at 7:21
  • $\begingroup$ @anongoodnurse I also looked at several papers on CA-MRSA, and non them mentioned anything about a growth rate advantage due to replication speed. They have different virulence factors, and are more adept at causing infections in otherwise health people, and the prevalence of these infections has increased dramatically in comparison to HA, but non mentioned the rate at which they replicate. $\endgroup$
    – AMR
    Oct 12, 2015 at 7:24
  • $\begingroup$ @anongoodnurse Incorrect usage was the bases of the OPs question. $\endgroup$
    – AMR
    Oct 12, 2015 at 7:27

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