What would be a microbiology blog without discussing antimicrobial resistance mechanisms or short AMRs?

Everybody has probably heard about them in recent news. But what exactly are antimicrobial resistance mechanisms and what are bacteria doing with them?

An introduction to antimicrobial resistance mechanisms

An antibiotic is a drug that inhibits bacterial growth. Generally, we use antibiotics to treat bacterial infections (useless against viral infections!).

The antibiotic binds to a target, usually a protein, inside the bacterium. This inhibits the target and prevents it from functioning.

There are different antibiotic classes meaning that antibiotics vary in their shapes and sizes. Therefore, antibiotics can bind to different targets inside a bacterium.

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. The bacterium eventually dies because it lost its outer protection.

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, the bacterium is called antibiotic resistant.

Where do antimicrobial resistance mechanisms come from?

Antimicrobial resistance mechanisms have two major sources.

An intrinsic resistance means that a bacterium is inherently or naturally resistant to a specific antibiotic.

Some antibiotics target specific components within a bacterial cell. However, bacterial cells are generally different. So, some bacteria might not have that specific target for the antibiotic. In this case, the bacterium is resistant to this specific antibiotic.

For example, the membranes of Gram-positive bacteria and Gram-negative bacteria are different. There are antibiotics that are specifically against either of them.

On the other hand, there are acquired resistances. This is when a bacterium does not naturally have the resistance against a certain antibiotic. But the bacterium can gain or acquire the resistance during its lifetime. This usually happens when bacteria mutate.

Another possibility is that a bacterium takes up genetic material/DNA from another already resistant bacterium. Then the bacterium gains the same ability as the resistant bacterium to fight off the antibiotic.

What are different antimicrobial resistance mechanisms?

Because not all the antibiotics work the same way, bacteria found different ways to get rid of them. Here, I will explain the best-studied mechanisms with pictures by the fantastic Laurent.

Reduced permeability

All bacteria produce transporters that import stuff from the outside into the cell. Some of these transporters also import antibiotics. And often a bacterium realises that antibiotics enter the cell via a specific transporter. In this case, the bacterium can produce less of this transporter.

Another possibility is that the bacterium mutates. Then the transporter 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

After an antibiotic molecule entered the cell, bacteria can also get rid of the antibiotic.

Bacteria produce efflux pumps. These export all sorts of cellular waste and some of these can export antibiotics. When a bacterium realises that there are antibiotics inside the cell, it produces a lot of these efflux pumps. With this, the bacteria export all the incoming antibiotics.

Changes in the antibiotic target

An antibiotic binds to its target very specifically and prevents the target from performing its regular function. Bacteria can change or mutate this target so that the antibiotic cannot bind anymore. This makes the antibiotic useless.

However, the function of the target is usually essential for the bacterium’s survival. So when changing the target, the bacterium needs to make sure to only prevent antibiotic binding and that the target itself still works perfectly.

Inactivation of antibiotics

Bacteria also found ways to get rid of the antibiotic itself.

For this, they developed pieces of machinery that either completely break the antibiotic or change the antibiotic slightly. Like this, the antibiotic cannot bind to its target anymore. In either case, the antibiotic becomes useless.

So far, researchers identified many different proteins in bacteria that can degrade or change almost all classes of antibiotics.

Biofilm

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 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. I also explain biofilm in more detail in this article.

The Joker – Multi-drug resistant bacteria

Now you know that there are different resistance mechanisms to fight off antibiotics. But, imagine one bacterium does not only have one of these resistance mechanisms but several!

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.

Antimicrobial resistances become serious

And new mechanisms are found every once in a while as well. Read here about how bacteriophages protect bacteria from antibiotics in a completely new mechanism.

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).

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.

