It's well-known that indiscriminate use of a drug leads to resistance. My question is what the limits on resistance are. It seems obvious that there must be limits: for example I can hardly imagine a tiger evolving "resistance to bullets", and similarly I can hardly imagine a microorganism evolving resistance to heat treatment @ 1000 degrees celsius (surely its proteins must long denature before then).

Are there methods of killing microbes that cannot be resisted? If so, can we make similar cannot-be-resisted drugs?

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    $\begingroup$ You mean drugs that eliminate bacteria without killing the host, right? Otherwise every strong enough poison is a candidate drug :D $\endgroup$ Jul 13 '18 at 8:30

There are physical limits to the existance of life forms, wether temperature, pressure, osmolarity, etc. But these are usually physicochemical fields acting over a wide spatial structure. In the case of drugs, they are physically localized molecular entities. They are usually very tiny, even compared to the smallest microbes. Even though the genome of any microbe is finite and they could not, in theory, recognize the infinitely many drugs we can synthesize (assuming the simple case they need one gene per drug resisted), they can just evolve very generic mechanisms like preventing these molecules to get into the microbe, pumping them out of the cell, or other generic mechanism; with the same overall effect: preventing the drug from acting in the desired way.

The question you ask is very interesting, and it is the focus of some recent efforts and discussions among academics. Here you can find a recent article discussing the possibility of "evolution-proof" drugs. As you can see, the subject is not trivial.



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    $\begingroup$ The article you link to discusses a very important and basic principle that you might include in your answer. In the absence of selecting pressure, the frequency of resistance shouldn't increase. Theoretically. $\endgroup$
    – De Novo
    Jul 13 '18 at 19:20
  • $\begingroup$ The link's dead ... any idea what the title was so I can try to find it? $\endgroup$
    – Allure
    Dec 24 '19 at 12:36
  • $\begingroup$ I just updated the link. Depending on your situation, you might need to access it through SciHub (using its DOI). $\endgroup$ Feb 1 '20 at 22:55
  • $\begingroup$ In case I need it again, the paper title is "Targeting virulence: can we make evolution-proof drugs?" by Richard C. Allen, Roman Popat, Stephen P. Diggle & Sam P. Brown. $\endgroup$
    – Allure
    Jul 7 '20 at 6:04

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