I'm curious how a plasmid that provide resistance would come to be, given there's no known evolutionary pressure towards it.
Could you elaborate on how you think such a thing might appear in nature?
Could you elaborate on how you think such a thing might appear in nature?
But some mechanisms of antibiotic resistance are relatively unspecific, such as multidrug efflux pumps.
Another mechanism could be that it arises de novo in some other bacteria, then spreads on a plasmid. In that case, resistance could happen from a very low probability event that only needs to happen in one bacteria, once, worldwide.
There will be, once the antibiotic is put into use. And that's assuming something working roughly the same way isn't, unbeknownst to us, already present in nature, leading to countermeasures also already being present in the environment.
> Could you elaborate on how you think such a thing might appear in nature?
The same way everything else does - natural selection. By random chance, some bacteria will survive the antibiotic treatment. Those bacteria will get to reproduce where their neighbors won't. Now, while it's possible many of the survivors will be left unharmed because their mutations made them completely broken and not worth the antibiotic's metaphorical effort, eventually there will be a survivor that's mutated just right to resist while being able to reproduce and thrive. Its lineage may still die off, but then maybe next one's won't, and now you have a resistant strain in the wild, possibly further spreading resistance-conveying plasmids.
It's a reasonable assumption that bacteria in the wild have been under pressure to increase the likelihood of developing resistance genes as an adaptation to organisms producing antibiotics in nature
This is a selective pressure that has been applied for millions of years and is likely the reason for anti-biotic resistance being able to develop independently over a relatively short timespan
With a synthetic class of antibiotics there would not have been a pressure to increase the likelihood of resistance genes developing against this particular class of drugs
As an example, soap and surface disinfectants have been in use for a long time, but to my knowledge resistance to those compounds have not develop in bacteria, despite being used much more frequently than antibiotics
As mentioned in another post, current antibiotics are already produced by organisms in nature, which has made bacteria more likely to develop resistance to those antibiotics over time
It's a reasonable assumption, that bacteria has evolved to be more capable of developing resistance, since having the ability for a resistance gene to a specific antibiotic to develop every X generations would provide a competitive advantage
This same pressure does not exist for the class of antibiotics presented in the article, so there has been no evolutionary pressure to select for genes that could potentially develop into a mechanism for resistance
So an effective antibiotic of this kind will handle a particular subset of cell walls, with particular properties, so it kills the pathogens without messing the patient up too much. That "subset" and "particular properties" is exactly the terrain in which evolutionary battles are fought. There is some corner of the configuration space your antibiotic is targeting, one that is reachable by the pathogen just through random mutations. Eventually, given enough chances to try, it'll find its way there.
"Doors and corners, kid. That's where they get you."