If you have a bad bacterial infection, what do you do? Go to the doctor and get antibiotics, of course. But, what if antibiotics don’t work anymore because the bacteria are antibiotic-resistant? In this lesson, learn how bacteria can become resistant to antibiotics and why this is such a big problem.
What Is Antibiotic Resistance?
It’s comforting to know that there are antibiotics. If you get a bacterial infection that gets out of control, you can just go to the doctor, get antibiotics, and get better. Right? That’s why antibiotic resistance is such a scary thing. Antibiotic resistance is when an organism that would ordinarily be sensitive to an antibiotic becomes resistant to it. Then, even something simple like an ear infection could turn out to be very difficult to cure.
In this lesson, we’ll learn about the problem of antibiotic resistance. We’ll learn how bacteria become resistant in the first place, and we’ll also take a look at why antibiotic resistance has become so prevalent in our world today.
Major Antibiotic Resistance Strategies
Bacteria have many different ways to avoid the effects of antibiotics. We’ll go through six of their general strategies and see an example of each one.
First, let’s imagine the bacterial cell as a castle in medieval times. We think castles are beautiful now, but they were also designed for defense against attacks. So is a bacterial cell, for that matter. The cell wall protects the bacterium against the hostile environment that it may find itself in, much like the sturdy fortress walls surrounding a castle.
In the face of attack, what would a castle do? Well, for one thing, it would pull up the drawbridges so that the invading armies couldn’t get in. Bacteria have a similar strategy to resist antibiotics. For example, in Gram-negative bacteria, antibiotics and other large molecules can only enter the cell through channels called porins in the outer membrane. These bacteria can become resistant to antibiotics if they restrict access of the antibiotic to its target by expressing fewer porins or by acquiring mutations that make the porins have smaller openings.
What if the armies were shooting cannonballs at the castle, though? Perhaps archers could shoot arrows at the people controlling the cannons, and in that way, stop the cannonballs from even getting near the castle. Bacteria do this in an even more clever way. They can secrete enzymes that destroy antibiotics. For example, one way to become resistant to penicillin and related drugs is to secrete beta-lactamases, which are enzymes that cut one of the chemical bonds in the drug molecule, which makes it ineffective. By the time the penicillin reaches the bacterium, it doesn’t work anymore.
Okay, let’s exchange our castle for a crowded party where lots of people are dancing and hanging out with their friends. But every so often, rowdy passersby crash the party and start picking fights. Luckily, there are security people that grab the troublemakers and send them back outside before they can ruin the party. Bacteria do something like this, too. They can express efflux pumps that remove antibiotics from the cell. This is a major way that bacteria can be resistant to tetracycline: they simply pump it out, which reduces the cytoplasmic concentration of the drug to levels where it’s ineffective.
All right, we’re going to use one more analogy to look at antibiotic resistance mechanisms: a kitchen that makes burritos. As we all know, burritos are crucial for human nutrition, and their most important ingredients are tortillas, rice and beans. Your burrito kitchen is well-equipped with all of these ingredients and more, until a terrible person comes and destroys your rice cooker. What are your options now? You could make burritos without rice, but that would be such a shame. Alternatively, you could make rice the old-fashioned way, on the stovetop. This would take a bit more effort and time, but at least you’d have your burritos.
How does this relate to bacteria? Well, some antibiotics disrupt bacterial metabolism by inactivating important enzymes that they need to make nutrients. For example, sulfa drugs inhibit a step in the pathway to make folic acid, an essential vitamin that bacteria need for their everyday functions. But, some resistant bacteria have developed different metabolic pathways that allow them to make folic acid even in the presence of these drugs. Like making rice on a stovetop, perhaps they can’t make it as quickly or efficiently, but they can still make it and survive.
Okay, apparently, rice cooker vandalism has become a big thing in our city. So to prepare ourselves, we could get lots of extra rice cookers. There wouldn’t be time to smash all of them before someone noticed all that noise in the kitchen. So, there would definitely be some rice cookers left unharmed. Bacteria use a similar strategy to this. They can overproduce an antibiotic target so that at least a certain percentage of the target enzymes will still work. This is a common bacterial strategy for resistance to sulfa drugs: there won’t be enough antibiotic molecules to inactivate all of the enzymes if the bacterium has made lots of extra ones.
The last strategy is to change the target molecule. In our rice cooker vandalism example, this would be like buying new rice cookers that don’t look like rice cookers at all. Perhaps they look like toasters! The rice cooker destroyer won’t even recognize them and won’t destroy them. Bacteria do this by acquiring mutations that change the structure of the antibiotic’s target molecule so that the drug doesn’t bind anymore. Bacteria can become resistant to many antibiotics in this way, for example by changing the structure of their RNA polymerase so that rifamycins can’t bind to it.
Alright, we’ve seen many different strategies that antibiotic-resistant bacteria use to avoid the effects of drugs. But, we still haven’t answered one major question, which is, how does a bacterium become antibiotic resistant in the first place? It has to acquire a genetic change that makes it resistant. This happens by chance: either the bacterium gets a random mutation, for example one that slightly changes the shape of a target molecule. Or, a bacterium can get an entire gene or even multiple genes for antibiotic resistance simply handed to it. This can happen in a process called horizontal transfer, where bacteria can exchange genetic material on plasmids, sometimes even with different species of bacteria. In this way, a bug can get a multi-drug efflux pump and start using it immediately. That was easy!
The Problem of Antibiotic Resistance
It wouldn’t be such a big problem if one or two bacteria causing your ear infection happened to be resistant to an antibiotic, right? After all, the vast majority of the bacteria would be killed off by the antibiotic.
The problem is that bacteria replicate super-fast. And, when an antibiotic is present, it’s basically survival of the fittest. Antibiotics put extreme selective pressure on a population of bacteria. Whichever bacteria happen to have resistance will survive and replicate to large numbers, while all of the others die off. It’s evolution on a very rapid scale. Now you still have an infection that’s harming your body, but it’s chock full of bacteria that don’t mind one bit if you take that antibiotic.
It’s only natural that bacteria evolve resistance to antibiotics. After all, they have to make a living, too. The problem is that they are becoming resistant faster than we are creating new antibiotics. And, misuse of antibiotics increases the selective pressure on bacteria and makes them become resistant even faster. What kind of misuse are we talking about here?
For one thing, too often, people take antibiotics when they have illnesses that aren’t even caused by bacteria. For example, when you have a cold or the flu, those are caused by viruses, and antibiotics won’t help at all. All they will do is select for antibiotic resistance among the bacteria you normally have in and on your body.
It’s also bad when patients do have a bacterial infection but stop taking their antibiotics as soon as they feel better, which is before all of the bacteria are killed. Patients should take all of the antibiotics that their doctor prescribes for them to reduce the number of surviving bacteria that are likely to have some resistance.
Another major problem is the antibiotics that are in animal feed. It turns out that including antibiotics in the food that is given to livestock prevents them from getting sick in the close quarters they live in and also helps them gain weight faster. Both of these give agricultural companies economic reasons to put antibiotics in their animals’ food. In fact, over half of the antibiotics that are used in the U.S. are not used for humans at all: they are used in animal feed. When a cow is on antibiotics for its entire life, of course, basically all of its bacteria will become resistant. Then, if people get bacterial food poisoning from eating undercooked beef, they’ll not only get sick, but be more difficult to cure because of the antibiotic resistance.
Let’s review. We’ve learned that antibiotic resistance is when an organism that would ordinarily be sensitive to an antibiotic becomes resistant to it. Bacteria can become resistant by acquiring genetic changes, such as mutations or antibiotic resistance plasmids, which can be exchanged between different bacteria in a process called horizontal transfer. Then, resistant bacteria are selected for when an antibiotic is present: it’s survival of the fittest.
We’ve learned six basic strategies that bacteria use to resist antibiotics. They can restrict access of the drug to its target by not allowing it to enter the cell. They can also secrete enzymes that destroy antibiotics, changing their chemical structure so that they are ineffective. Bacteria can also use efflux pumps to remove antibiotics from the cell.
In the case of antibiotics that disrupt bacterial metabolism, resistant bacteria often develop different metabolic pathways to allow them to still produce the metabolites they need to survive. Or, they can overproduce the antibiotic’s target so that the antibiotic won’t be able to reach high enough concentrations to inactivate all of the copies of the target molecule. Bacteria can also acquire mutations that change the target molecule so that the antibiotic can’t bind to it anymore.
Finally, we learned that antibiotic resistance develops more quickly when antibiotics are misused, because this increases the selective pressure that the drugs put on the bacteria. Examples of the misuse of antibiotics today include using antibiotics unnecessarily, stopping antibiotic treatment too early, and overuse of antibiotics in agriculture.
After you’ve completed this lesson, you’ll be able to:
- Describe six ways that bacteria develop antibiotic resistance
- Identify the process of horizontal transfer to antibiotic resistance
- Explain several ways that antibiotics are misused and how that misuse leads to antibiotic resistance