How do bacteria become resistant to antibiotics?

You probably have already heard about the problem of antibiotic resistance. We are talking about a situation in which bacteria from all over the world are becoming more and more resistant to our antibiotics (the only way we have to kill them if necessary). And this is not only a problem into the health department but has big ecological influences.

Let’s start from the beginning, how can this problem arise?

That’s super easy: evolution. Bacteria are constantly evolving, so abundant exposition to antibiotics will permanently create a selection for resistant bacteria. In particular bacteria can develop resistance through point mutation, homologous recombination and conjugation (horizontal gene transfer). In fact, once the resistance has arisen, not only the resistant will be selected, increasing in frequency in the next generation, but the resistance gene can be transferred to another bacteria. This can actually generate multiple resistance strains that are really, but really, hard to kill.

A timeline of antibiotics resistance, and how it has been a known problem for a long time. Source The antibiotic resistance crisis.

Who’s responsible for this problem?

But let’s get some more insights on the process. Is this process a problem that we caused? Is that even a problem after all? Well, if we just understand that evolution is the cause, then we immediately get that this process is inevitable. Exactly, you can’t stop evolution. Just for the nature by which the world works resistant bacteria will always develop. This is not a problem in its principle, it’s just a natural phenomenon that became a problem because we were careless and now we don’t know how to handle it anymore.

Actually, if you pick random samples of soil bacteria from your garden, chances are pretty high that most of them are resistant for many antibiotics. This is true just because many of our antibiotics that we use, are just borrowed from bacteria themselves. Yep, another example in which we steal from bacteria!

Antibiotics are just weapons that bacteria use to kill each other’s

Bacteria in the wild are competing between each other. To better survive they produce antibiotics and hence they create a force in the environment to develop resistant bacteria. But things are even worse: bacteria have even been shown to be able to actually live on, i.e. striving by eating, antibiotics! Yes some soil bacteria can eat and survive only on antibiotical diets, eliminating the molecules from the environment.

Theory predicts that in absence of antibiotics, thus selective pressure, being a resistant mutant is not advantageous. This is because if you keep mutating even in absence of antibiotics, sooner or later you will accumulate a deleterious mutation that will reduce your fitness. So why so many bacteria are resistant even in the wild?

Well a study found that viral pressure can develop high mutation rates in bacteria. So bacteria keep mutating as another defense mechanism against virus! But even worse, another study suggests that mutators (bacteria with high mutation rates) that develop resistance have actually higher fitness compared to the ones that don’t have resistance!

What can we do?

So antibiotics resistance is not really a recent/new or a surprising problem. It was actually to be expected, considering that we find new antibiotics molecules very slowly. So what can we do to tackle this issue?

Well, it’s nice to notice that in matters like these, branches like evolutionary ecology, a generally more theoretical field, can actually provide help and solutions. After all, we’re talking about evolution.

Besides using fewer antibiotics and using different mixtures of existing molecules; using different tactics of cycling and mixing, we can use different, sometime more extreme approaches.

A new era of antibiotics, for example, is aiming to disrupt bacterial communication, called “quorum sensing”, into ecological population that exist everywhere. If we find such a disruptor than bacteria can’t communicate and thus they can’t be as effective in creating an infection. So this, counterintuitively, doesn’t aim to kill bacteria but just to keep them there, unable to talk to each other. This approach would work because will block evolution of resistant strain almost totally. How? Well, try to imagine I can speak only English, and every other bacteria can understand and speak only English. Now I have pollution in the environment that impede us to talk in English. The only thing we can do is to stay isolate and don’t talk anymore, unless you evolve a mutation “for another language”. But even in this case evolving the ability to speak Spanish won’t help, because anybody else in the population can’t understand it! This creates a lock-proof system to prevent resistant strains. Evolving resistance mutations is simply not convenient!

Another extreme tactic is to use viruses! Playing with the aggressiveness of bacteriophages we can either drive them crazy so that they can kill all the bacteria, but they can stay healthy for us, or we can drive them really “lazy” so that there will be no selective pressure to have many mutators in any given bacteria population.

Many more aspects need to be described on this problem, but for now, I think it’s already nice to say that evolutionary ecology can give us solution to health problem. So that, despite what people think, fundamental ideas in biology can change and save the world.

Didn’t know evolution could influence so much our existence? While you think upon it, let me tell you another story…

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