(Some) antibiotic compounds are produced by fungi - presumably to defend themselves against bacteria - some bacteria have evolved resistance to those antibiotics compounds - surely what would be expected to happen next would be for some fungi to stumble upon a different antibiotic ompound that still works.
Can’t we make this happen, or at least provide the ideal laboratory environment in which it could happen under our noses, in order to produce new, effective antibiotic drugs? - Keep exposing lots of mould cultures to antibiotic-resistant bacteria and keep checking for survivors.
Or are we actually doing this somewhere, and I just didn’t know about it?
The trouble is the timescales. Evolution works because of long time scales, and while bacteria and fungi don’t take long to reproduce, you would still need thousands (or even millions) of generations to get the right mutation - cause it’s random, and it’s maybe one base in the entire genome that would have to change. Assisted selection is faster, but if we can’t find any sources with appropriate resistance to start with, it’s hard to select and breed.
So it is actually much faster for the biochemists and chemists to create antibiotic chem-alikes and test those, or determine specific bacterial chemical processes to attack. Genetic algorithms can be used with computer models to produce new possibilities, but then compounds actually have to be synthesised and tested.
Si
Hmmm… I wonder then if we ought to be sampling wild fungi from locations that have been exposed to resistant bacteria (sewers, perhaps?) - see if nature has already stumbled on a fix.
I recall reading some years ago that the Russians had some success with phages; viruses that infect and kill specific bacteria, and evolve as fast or faster as the bacteria. Unfortunately, last I heard the research pretty much stagnated after the USSR fell, due to a lack of funds.
Of course, the major problem with antibiotics isn’t finding chemicals to kill pathogens. It’s trying to find the chemicals that kill the pathogens AND don’t kill you (too much).
Something like that has been done (wiki article) Fleas, smaller fleas ‘n’ all that. But there seem to be difficulties. From that article
Oops.
You can certainly screen for new antibiotics using resistant strains of bacteria - plant extracts are routinely screened against VREF or MRSA to look for new antibiotic compounds. There is no evolutionary component to this approach though. Antibiotics are small molecules, by and large, and applying selective pressure to the biosynthetic pathway by which these molecules are assembled is very difficult, although in principle not impossible; google ‘combinatorial biosynthesis’ for some examples.
Where you can use evolutionary methods very effectively is with biomolecules such as proteins. Molecular biology gives us reliable, general techniques to over-express and mutate most proteins at will. Say you had a protein that had average antibiotic activity - many examples exist but they would make lousy drugs unfortunately. It is possible to overexpress a thousand membered library of mutants of this protein using techniques that introduce errors into the gene sequence. Screen these mutants against MRSA and pick the handful of colonies that are active. These then are the basis for a second round of mutation, where you make another 1000 mutants and so on. After 6 or 7 rounds of mutation you could in theory have a world-beating MRSA killer. The technique is called ‘directed evolution’.
I am not sure that the idea of using a protein that people could take as an antibiotic drug has any mileage in it. Certainly, biologicals have made a massive impact in pharmaceuticals in recent years, things like antisense DNA, monoclonal antibodies etc. Maybe it is not too far fetched to think of some sort of antibiotic protein.