This episode is brought to you by the Music for Scientists album,
now available on all streaming services.
To start listening, check out the link in the description.
[ intro ]
You might have heard that, in less than two days,
one bacterium could make enough copies of itself to outweigh the Earth.~
And that’s true! Bacteria can grow at terrifying speeds
when they have enough resources. In fact, basically the only reason
they don’t take over the world is because they spend most of their time starving.~
And what’s really interesting here is how they survive a life of starvation.
Their secret is that they poison themselves, and researchers are finding inventive ways
to use those poisons to our advantage. And to visualize just how fast bacteria can grow,
let’s consider our good friend E. coli — that sometimes harmful, but usually friendly
microbe found in our guts, among other places.
Each bacterium can create a copy of itself every 20 minutes.
So, in terms of mass, you go from one picogram to eight within an hour.
Keep that growth going, and after just 24 hours, you have 4.7 billion grams of bacteria.
Continue through 44 hours, and the mass of microbes equals the Earth.
And in 48, it would weigh the same as all of the planets in the solar system combined.
Of course, between two days ago and right now, that didn’t happen.
And it can’t happen, because there just aren’t enough nutrients available for bacteria
to keep up with that super fast rate of growth. And when bacteria realize that resources
are running low, they get stressed out.
So, they slam on the brakes to slow their growth and activity way down.
That brake-slamming includes some pretty toxic behavior.
And I mean that literally. Like, a bacterium might make toxins which chop
up its genetic instructions for making proteins; Or, ones that make its protective
membrane unstable. One way or another, these
toxins hinder its ability to grow or reproduce. And a really stressed-out bacterium can even get
overwhelmed by toxins that it creates — even though it has the antidotes!
You see, these toxins are part of what scientists call toxin-antitoxin
— or TA — systems. In most of these systems,
bacteria are always making self-poisoning toxins that they code for in their own DNA.
But, when the bacteria are not stressed, they also make antitoxins
that interfere with those toxins in some way. It’s a genetic buddy system.
The antitoxin sticks around to prevent the toxin from making a mess.
For instance, it might prevent the toxin from being made,
either by camping out on the DNA right in front of the toxin’s gene
or intercepting the genetic instructions for it so they don’t reach the cell’s protein factories.
Or, it might latch on to the toxin itself and block it from causing trouble.
But antitoxins are more fragile than the toxins they hinder,
so in a stressful environment, they fall apart first. Then, the toxins have free rein.
And while that might sound bad for the microbe, it’s actually important for it to slow
its roll when there’s not enough food. Not having enough nutrients to fuel everything our
cells have to do is why starvation kills us — thanks to these toxins, bacteria can simply relax
and survive until the getting’s good again. Now, microbiologists have identified thousands
of kinds of toxins in the almost 40 years they’ve been studying TA systems.
And, they’ve also uncovered some ways to hack these systems for research.
Take the ccdAccdB system, which can block the bacterium from reading its own DNA.
If the cell is happy, then the antitoxin ccdA will hold on tightly to the toxin, ccdB,
and prevent it from causing trouble. But if ccdB is on its own, then it goes after
a protein called DNA Gyrase. You see, when a bacterial
cell wants to read its genes, it has to untwist its genome and unzip the two
strands of DNA that form that iconic helix. All this causes twists to pile up —
the tension from which, eventually, would damage the DNA.
DNA Gyrase relieves this tension by strategically snipping the DNA
and letting it unwind a bit before it’s stitched back together.
But, when ccdB attacks DNA Gyrase, it jams it, locking it in place.
This physically blocks the gene-reading machinery and prevents the broken DNA from being fixed.~
All of which, obviously, isn’t great for the bacterium.
But it’s pretty great for scientists that want to genetically engineer microbes,
because they can use it to make sure that bacteria have the genes that they want them to have.
First, they take a strain of bacteria that doesn’t have the ccdBccdA pair.
Then, they make a small loop of DNA that has the toxin, ccdB,
and resistance to ampicillin, an antibiotic. Now, if just they gave the bacteria just this,
they’d be between a rock and hard place. When ampicillin is added, everything
without the DNA loop dies. But everything with this new DNA
has ccdB and no antidote, so they die, too. But ccdB is actually just a placeholder!
Bioengineers can strategically swap it out for whatever interesting gene they want.
Though, the process isn’t perfect, and since DNA is so small,
they can’t really see if it’s worked — which is why the toxic gene is there in the first place.
They know that only bacteria that have the whole, correct loop, including the new gene in place of
ccdB and the antibiotic resistance gene, can survive when they blast
them with ampicillin! And researchers are hoping to take TA
systems even further, into medical research. Some experts think that they could be
used to create new antibiotics — the idea being that, since bacteria
are already making these deadly toxins, maybe we could take advantage of that to
selectively harm the bacteria that make us sick. For example, the bacterial disease tuberculosis
has been especially hard to treat with vaccines or antibiotics,
but the bacteria have a bunch of TA systems. So, maybe, researchers can design a drug that acts
like a “decoy” toxin to distract their antitoxins, allowing their built-in toxins to kill them.
Of course, succeeding in that will require a much deeper understanding of these systems
and how they look in different bacteria. And scientists are still teasing out a lot of the
details of exactly how they work and what kinds of stresses bacteria may have evolved them for.
Still, we can be kind of thankful that bacteria keep themselves from
gobbling up every resource available. Because, in the end, the very same things
that keep them from taking over the world may give us new ways to keep them in check!
When I think about it, there’s something kind of elegant about these self-limiting TA systems.
And that’s exactly the kind of elegance that inspired Patrick Olsen
to write and record the Music for Scientists album!
He was also inspired by the people of science
who help us fully appreciate the world’s beauty by allowing us to understand it.
You might want to check out the song ‘The Idea’.
It’s all about how the process of science and figuring out how the world works is hard, a
nd for every right idea, there are also an infinite number of wrong ones.
And the music video is stunning! You can find it at the link in the description.
[ outro ]