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Thx so much for the video.

I am very confused though ... the documentary implies that the bacteria are developing the immunity through evolution ... over millions of cell divisions. But how can this be happening so fast? If a bacteria were to be countering the antibiotic via an enzyme, it would take an insane amount of time to develop that enzyme by pure chance. It is more likely that some of the bacteria already had the anti-antibiotic enzyme and we're seeing selection in progress. Can someone please please explain?



When I was doing some molecular genetics on E. Coli in the summer of 1977 I was told that for many antibiotics, 1 in a million of them would spontaneously mutate and develop resistance if exposed, and 1 in a billion for streptomycin.

Note that there are many methods of antibiotic resistance, including little pumps that try to keep the level low enough inside the bacterium. They've been developing them for a very long time, the other insight you need into this is the ecological one.

Most are from molds, and they release them to better compete with bacteria. And a resistant bacterial strain will not necessarily compete well with others lacking its mechanism(s) because those are otherwise maladaptive . E.g. it's spending raw materials and energy producing a β-lactamase while its competitors are dividing more rapidly. Only when you add the selection pressure of the antibiotic does it win big.


There's also a strong role for horizontal gene transfer in antibiotic resistance, e.g. by swapping plasmids, which can allow bacteria to swap higher-granularity mechanisms, rather than having to evolve them from scratch with random mutations.


This feature is basically bacterial sex and turns their evolution from a slow serial computation to a highly parallel computation that gives an exponential speedup in evolution.

I think this effect is the extremely under appreciated benefit of sex/exchanging dna.


It's a good question. Maybe that is what they are trying to figure out?

I've heard suggestions that the mutation rate can go up in a high-stress environment, perhaps that could be related?

I hope the HN research effect kicks in and someone finds and summarizes the research on these questions.


Amplifying on my answer in this subthread and I now see mjn's comment, it's complicated. Simple mutations only take you so far, they change something that's necessary for the antibiotic to work. E.g. a surface protein that brings it inside gets trashed, or a enzyme or structure that it works against changes enough to be resistant while still functioning enough for survival.

The nastier stuff, like β-lactamases---enzymes that destroy the β-lactam ring that is the "active ingredent" of so many antibiotics ... and that it's used by so many families that humans can tolerate is telling---are obviously a lot more sophisticated. Bacteria developed them to compete with the molds that produce β-lactam antibiotics, and they spread from one species to another, especially in plasmids as the article notes.

A great deal of this is not new mechanisms of resistance being developed, but long existing ones becoming prevalent. Somewhat like in the good old days when a drug company could make its money back bring an antibiotic to market, and scouring the globe for molds that produced ones, improper use of antibiotics (e.g. not switching to one of different mechanism quickly enough, especially likely in places like India where they're in practice available over the counter) plus widespread global travel is allowing the best mechanisms to survive and sort of thrive.

Not thrive in most environments of course, just in humans who are under the selection pressures of antibiotics.




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