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If I use antibiotic on a specific type of bacteria, some will survive because it is resistant. Was this bacteria resistant to this antibiotic before it was even used, or did the bacteria develop resistance after the antibiotic is used?

How or why some bacteria can simply mutate to form beneficial alleles which will help in survival and others can't?

Maxim Kuleshov
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Antibiotic resistance comes from selection pressure: any bacteria that are resistant will survive and replicate, so in the next generation of bacteria you will find more resistance.

Bacteria do not simply mutate to form beneficial alleles, the alleles or genes that confer drug resistance must already be in the population; by using antibiotics, however, you're killing off their competition by killing the bacteria that don't have the resistant allele(s)/gene(s).

It's very unlikely that one individual using one antibiotic for one illness will lead to detectable antibiotic resistance. However, antibiotics aren't used in just one individual: they are used repeatedly, in many individuals, often in multiple species, etc. It is this broad use of antibiotics over time that eventually "finds" strains that are antibiotic resistant. Once these strains with resistant alleles become more prevalent, it becomes more likely that they will be present in some quantity to be selected for in the future.

Bryan Krause
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    Not that you said otherwise, but I'd like to emphasize that there need not be a dichotomy between complete resistance and no resistance. Some population with partial resistance could have a selective advantage, especially if the antibiotic dose is low (or short), and then continue to mutate towards higher resistance. – canadianer Jan 02 '19 at 19:37
  • @canadianer Of course, I think this is a fortunate case where we've actually picked a linguistically informative word as a scientific community: resistance refers to being less susceptible to the antibiotic, that is, resistant to it, rather than invulnerable to an antibiotic, and so resistance to a given drug can be on a spectrum. It could be thought of as just a shift in the LD50 for a given drug. – Bryan Krause Jan 02 '19 at 20:35
  • I think there is too much emphasis on alleles in this answer. Resistance to antibiotics is not a purely genetic phenomenon. Some cells may resist the antibiotic pressure through epigenetic mechanisms, e.g. upregulation of efflux pumps etc. There need not necessarily even be a specific mutation required. – Joe Healey Jan 02 '19 at 20:39
  • @JoeHealey I'm not sure I follow. An ability to upregulate of an efflux pump is going to be due to some allele, an epigenetic mechanism is just that: a mechanism. If one organism has a different propensity towards epigenetic modification of an efflux pump, that's still an allele. – Bryan Krause Jan 02 '19 at 20:47
  • @BryanKrause an allele is specifically a variant form of a gene, but the efflux pumps (or whatever other mechanism we are discussing) may only be deployed differentially - any mutations arising (which isn't always necessary) need not even be in the gene, so calling this an allele isn't wholly accurate. So, one bacteria that is killed, may simply not have responded sufficiently to the selection pressure and therefore dies, whilst another cell survives. The response could be affected by any number of other things going on in the cell such as quorum signals, nutrient levels etc. – Joe Healey Jan 02 '19 at 20:53
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    For me 'must already be' sounds confusing. When did 'already happen? Are you talking about already drug-resistant strain (if so - where did it come from?), or any mutation that happened to happen at moment when antibiotic was poured over, or, let's say, plasmid? – Maxim Kuleshov Jan 02 '19 at 20:56
  • @JoeHealey We're talking about evolution of gene resistance, not the variables that affect survival of individual cells and cause not all cells to die exposed to the same drug. If it isn't heritable it isn't meaningful to drug resistance. The allele need not be in an efflux pump, it could be a regulator. I suppose using a very strict definition of allele you could say that "allele" cannot refer to insertions of additional genes, etc, but I feel like that sort of terminology is unnecessarily pedantic and leads people astray to the idea of "gene for A, gene for B." – Bryan Krause Jan 02 '19 at 20:56
  • @MaximKuleshov All of the above. – Bryan Krause Jan 02 '19 at 20:57
  • @BryanKrause I'd disagree with "if it isn't heritable, it isn't meaningful". With the question as posed, it is meaningful if it allows at least some cells to persist through that specific round of selection, leaving at least some of the population viable on the 'other side'. What happens beyond then is anyone's guess, but the population has survived, and will almost certainly have used many different 'dirty tricks' over as many rounds of selection as it takes in order to survive. You don't necessarily suddenly get resistance and have it hang around forever, its much more fluid than that. – Joe Healey Jan 02 '19 at 21:00
  • @JoeHealey If it isn't heritable, no additional resistance is carried to the next generation, and no selection has taken place. What happens beyond then isn't just anyone's guess, it would be the only thing that matters (beyond the effects of the infection on the individual we're talking about). If the "dirty tricks" are heritable then there is some gene/allele there mediating that dirty trick. Even if it's epigenetic, as long as it's heritable it counts. – Bryan Krause Jan 02 '19 at 21:02
  • @BryanKrause from the perspective of any single cell, I agree. But from the perspective of a population persisting through selection, the resistance does not need to be inherited. It can re-emerge on each exposure (though I concede this is less efficient and therefore less likely). Selection has taken place because the population will have been bottlenecked by the fact that many cells will not have survived. – Joe Healey Jan 02 '19 at 21:07
  • @JoeHealey Starfishes (at least some of them, not sure of the exact extent) can regrow limbs that are removed. We do not say that starfishes that do not have their limbs removed lack the arm regrowing trait just because they haven't had any limbs removed. A population that has an ability to upregulate a pump for resistance has a resistance trait that has to be encoded by some heritable factor. The difference between that population and a population that does not have that ability is a gene or allele. – Bryan Krause Jan 02 '19 at 21:09
  • I think that's a bit of a false equivalency, but perhaps we will just have to agree to differ on this one. I still believe that playing fast and loose with the term 'allele' is not a triviality - terminology exists for a reason. – Joe Healey Jan 02 '19 at 21:15