What would be a microbiology blog without discussing antimicrobial resistances or AMRs? Everybody has probably heard about them in recent news, but what exactly are they and what is the problem with them?
So far I have only written about the amazing and fascinating sides of bacteria – and there is yet more to come! However, now we are going to start talking about their nasty side by explaining what antimicrobial resistances are and why they are such a challenge.
But as always I will start by introducing a couple of phrases and concepts to understand this article better.
An antibiotic is a drug that inhibits bacterial growth and is used to treat bacterial infections (useless against viral infections!). The antibiotic binds to a target, usually a protein, inside the bacterium and prevents the normal functioning of this target. For example, some antibiotics bind to machines that produce the cell membrane. When the antibiotic binds and inhibits these machines, the cell membrane can not be produced properly anymore. The bacterium eventually dies because it lost its outer protection.
The specific target of an antibiotic depends on chemical properties of the antibiotic molecule. There are different antibiotic classes so that antibiotics vary in their shapes and sizes. Therefore, they can bind to different targets inside a bacterium. If an antibiotic has a target within a bacterium and can harm the bacterial cell, this bacterium is called antibiotic sensitive. If however, an antibiotic does not have an effect on a bacterium, it is called antibiotic resistant. In this case, the bacterium carries a resistance of which two classifications exist.
Some bacteria contain an intrinsic resistance against certain antibiotics, which means they are inherently or normally resistant to a specific antibiotic. For example, bacterial cell membranes are formed of different components and some antibiotics target specific components within a cell membrane. If a bacterium does not contain this specific component, the antibiotic can not inhibit this component and the bacterium is resistant to this specific antibiotic.
Gram-positive bacteria only contain one thick cell wall while Gram-negative bacteria have two thinner cell membranes. There are antibiotics that are specifically against either of them.
If a bacterium generally does not have the resistance against a certain antibiotic, but gains or acquires it during its lifetime, it is called acquired resistance. This can happen when a bacterium spontaneously mutates, which means it changes its DNA. Another possibility is that a bacterium takes up genetic material/DNA from another already resistant bacterium, a mechanism which is called horizontal gene transfer. With this, the bacterium gains the ability or the machinery to fight off the antibiotic.
Both mutation and horizontal gene transfer can be triggered when bacteria are treated with low concentrations of antibiotics. In this case, the bacterium is getting prepared to be hit with more antibiotics so that it quickly adjusts to the new incoming danger. So at the end, antibiotic resistance is just a bacteria’s way to survive the danger that comes from antibiotics – their survival strategy.
As there are different antibiotic classes that have different targets within a bacterial cell, bacteria found different ways to get rid of the antibiotic danger. Here, I will explain the best studied mechanisms with the help of some little pictures, for which all the credit goes to my fantastic previous colleague Laurent.
- Reduced permeability
Bacteria produce transporters that import all sorts of stuff into a bacterial cell, as for example iron. These transporters can also import antibiotics. If a bacterium realises that antibiotics enter the cell via a specific transporter, the bacterium responds by producing less of this transporter. Another possibility is that the bacterium mutates and produces a transporter that can still transport its normal substrate but not the antibiotic anymore. With this the bacterium makes sure that the antibiotic never actually enters the cell.
- Increased efflux
Instead of making sure that the antibiotic never enters the cell, bacteria also found ways to get rid of the antibiotic once it is inside the cell. Bacteria generally produce so called efflux pumps that export all sorts of cellular waste and these also export antibiotics. So when a bacterium realises that there are antibiotics inside the cell, it produces a lot of these efflux pumps to make sure that all the incoming antibiotics are transported to the outside superfast.
- Changes in the antibiotic target
Most antibiotics bind to their targets very specifically and prevent the target from performing their regular function. Some bacteria can change or mutate these targets so that the antibiotic does not bind anymore and becomes thus useless. However, this is a bit tricky, because usually the function of the target is essential for the bacterium’s survival. So the bacterium needs to make sure that when changing the target only the antibiotic binding is prevented and the target itself still works perfectly.
- Inactivation of antibiotics
Another way to fight off of the antibiotic danger is to get rid of the antibiotic itself. For this, bacteria developed machineries that either completely break off the antibiotic or they change the antibiotic just slightly so that it cannot bind to its target anymore. In either case, the antibiotic becomes useless and the bacterium is safe from the harm of it. So far, many different proteins have been identified in different bacteria that can degrade or change almost all classes of antibiotics.
Some bacteria have the ability to form a so called biofilm, which is basically a lot of slime in which bacteria can live and grow. This slime is like a house that protects from the rain, so no antibiotic can enter and all the bacteria inside this house/slime are protected. The formation of biofilm is not an antibiotic resistance mechanism per sé because bacteria build biofilms to be generally protected from all sorts of environmental dangers. A comprehensive article about bacterial biofilms will probably follow at some point.
- Multi-drug resistant bacteria
Now that we discussed that different resistance mechanisms exist to fight off antibiotics, imagine one bacterium does not only contain one of these resistance mechanisms, but a few of them! So even though we have a lot of different antibiotics available, bacteria learned how to get rid of most of them! This is what they call a multi-drug resistant bacterium as they are resistant to many different antibiotics.
This is a serious problem as you can imagine. If we do not have any more drugs to fight bacteria, they will just keep making us sick. This will eventually lead to more and more deaths caused by bacterial infections (sorry to sound so harsh). So, based on this, everybody should be conscious of when and how much antibiotics they take when they are sick or whether they just let their immune system do its job.
And this is why research is so important. One major challenge for scientists right now is to find alternative anti-microbial drugs to which bacteria cannot become or hardly become resistant.