how bacteria can natural select to become resistant to antibiotics in decades but not resistant to heat (cooking), ethanol (fermentation), and/or salt after tens of thousands of years of contact w these pressures.

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Why is cooking still an effective way of eliminating human pathogens or fermentation or salting? These methods do not eliminate all traces of the bacteria so what is keeping a random mutation from happening that allows, say, e. Coli in beef to become resistant to heat up to 60c or Listeria to resist salt concentrations to the same levels as bacteria which are not infectious and potential beneficial to us that can tolerate?

What is it about antibiotics that makes them so susceptible to creating these random mutations that antibiotics become near obsolete in decades?

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It’s easier to evolve defenses to antibiotics than the other factors. So even though there has been more time either the steps needed to mutate are much much more difficult and haven’t happened yet OR there is just not way to evolve around the problem.

Antibiotics interrupt various processes in the cells, like a tree falling on a train track blocking a particular train route. Antibiotic resistance is like using an alternate route so the tree isn’t an issue anymore.

Heat affects the proteins that are part of the cells more directly. It doesn’t block a process from happening, it causes the proteins that do the process to fall apart. To go back to our train example it’s like the power going out completely. Now it’s not just one route that’s not working, the whole system can’t function. It’s a lot harder to adapt to that. Some proteins are more resistant to heat than others so in theory if they can do the same job it might be possible to develop resistance, but there are still limits on how much heat proteins can handle due to basic physics and chemistry.

The main difference is that antibiotics (usually) work through more complex chemical reactions, while the stuff the bacteria don’t get resistance to are very simple.

On an ELI5 level: Humans can train their bodies to be stronger and fight other humans and animals better . But you can’t train against being crushed by a 16 ton boulder.

As a more accurate example, lack of resistance against heat: Heat is just energy, and the only way to “resist” it is insulation. But insulation usually needs to be thick to be efficient, so bacteria can’t do that. And if a bacteria gets heated up, let’s say to 110°C, then the water inside will boil and blow up the bacteria.

On the other hand, antibiotics like penicillin use complex chemical reactions to kill the bacteria/prevent them from multiplying. Therefore by slightly altering their structure the bacteria may change so that penicillin can no longer undergo this chemical reaction with them, giving immunity.

Heat and salt both directly affect the core functions of life, meaning it is extremely difficult for a single form of life to evolve to handle wide ranges, and those difficulties are amplified for smaller life forms (eg bacteria) than for larger ones (eg mammals).

Notably, heat affects water state, protein structure, and the speed of chemical reactions. This means the basic chemistry of life needs to be different at different temperature ranges, and those that work well at higher temperatures are much less suitable for lower temperatures. There are bacteria and fungus that live in hot springs, called [Thermophilic Bacteria](https://www.nps.gov/yell/learn/nature/thermophilic-bacteria.htm), and are one of the main factors giving Yellowstone hot springs their characteristic colors, however they cannot survive at the more “normal” temperatures that we live at.

Salt has similar major effects in the behavior of chemistry, and most life can only survive with fresh water or salt water. All life needs some amount of salt for proper functionality, and thus it cannot be completely blocked out. A handful of larger organisms can manage to switch between the two, but not many – they are called [euryhaline species](https://en.wikipedia.org/wiki/Euryhaline). There is actually life that lives in [briny water](https://en.wikipedia.org/wiki/Brine_pool#Microbial_diversity_and_community_composition), which is much saltier than sea water, but it will die in fresh water. The wider the spread of salinities, the harder it is for a single life form.

Antibiotics, on the other hand, interfere with specific functions of the bacteria and are not core to the basis of life. As such, it is easier for mutations to block uptake of a specific antibiotic as the core functions of their life do not rely on the uptake of that specific chemical. Such evolution is typically based on slightly changing the shape of specific receptors on the outside of the cell or slight tweaks to the proteins that transfer chemicals into the cell.

A lot of bacteria have evolved the ability to survive in those extremes. Look up extremophiles.