2 How do bacteria become resistant to antibiotics?

The ability to divide rapidly and reproduce exponentially means that bacteria are constantly mutating and adapting to survive any changes in their environment. Antibiotic resistance is the ability of bacteria to resist the action of antibiotics so that they survive exposure to antibiotics that would normally kill them or stop their growth (CDC, 2017; PHE, 2017).

You could be forgiven for thinking that antibiotic resistance is only caused by human use, and misuse, of antibiotics. However, as you will see in the following video, bacteria that have not been exposed to antibiotics used by humans have acquired resistance to many of the antibiotics we use to treat infections; as you will see later, some may be inherently resistant if they lack the pathway or component that the antibiotic acts on: for example, colistin has no effect on Gram-positive organisms, because they do not have an outer membrane. This video also appears in The problem of AMR, where it was included to show the ubiquity of antimicrobial resistant bacteria. We include it again here so that you can begin to think about the mechanisms that give rise to AMR, which you’ll learn about below.

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Transcript: Video 2 Antibiotic resistance is a natural bacterial defence mechanism.

MICHAEL MOSLEY:

It was in 2012, in a cave much deeper than I'm able to go, that Hazel's team made their breakthrough discovery.

HAZEL:

So the kind of areas that we sample look quite a bit like this.

MICHAEL MOSLEY:

Hazel took a bunch of bacterial samples from the cave and sent them off to a lab for analysis. The results shocked everyone.

HAZEL:

So I sent him just 100, and he started testing them. And he's like, you're not going to believe this, but they're resistant to everything. Everything that's used.

MICHAEL MOSLEY:

So these were bacteria you found on a wall in a cave.

HAZEL:

Much, much more remote than this, much further way.

MICHAEL MOSLEY:

That had not seen humans for...

HAZEL:

We know humans had never been in there because we have the exploration records. So there was no impact on it. And they were resistant to practically every antibiotic that's used in the clinic.

MICHAEL MOSLEY:

That is both incredibly exciting and incredibly scary. Nobody had ever thought that you would find resistant bacteria down at the bottom of a bloody cave.

MICHAEL MOSLEY:

They’ve had no interaction with humans. But the bacteria Hazel found in the cave were resistant to a huge array of antibiotics we use in modern medicine. This resistance had clearly evolved over millions of years without us having anything to do with it. Why?

Well, it makes sense when you think of antibiotics not as man-made, but the byproduct of war between microbes. They make chemical weapons to destroy their enemies and steal their resources, weapons we have learned to exploit as antibiotics. The bacteria living deep in the cave have had millions of years to evolve weapons that can target and destroy even their toughest rivals. The battle for scarce resources, like nutrients and energy, is particularly brutal down here in the caves.

HAZEL:

It's really starved down here. There's no resources. It's probably one of the most starved environments on Earth. Because if you think about it, any energy needs to come in through the rock. And so there's a big competition for nutrients.

MICHAEL MOSLEY:

The fewer the resources, the more intensely the microbes battle. And that creates resistance. Because the bacteria under attack don't just lie back and die. When billions of bacterial cells are bombarded, all it takes is for one cell to mutate its DNA in such a way that the antibiotic can no longer kill it. This ability to resist then spreads fast. So developing resistance to antibiotics is an entirely natural process which the bacteria of Carlsbad have taken to the extreme.

End transcript: Video 2 Antibiotic resistance is a natural bacterial defence mechanism.

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Video 2 Antibiotic resistance is a natural bacterial defence mechanism.

As you may now realise, many antibiotics in clinical use have originated from substances used by micro-organisms to defend themselves against other micro-organisms. In essence, humans have taken these important molecules and made use of them to produce the antibiotics we use. It therefore makes sense that bacteria would derive ways to defend themselves from antibiotics.