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Duration:07:23
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This episode is brought to you by the Music for Scientists album! Check out “The Idea” music video here: https://www.youtube.com/watch?v=tUyT94aGmbc.

Given just a little time, bacteria could outgrow earth, so what's stopping them?

Hosted by: Rose Bear Don't Walk

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Sources:

Sources:
https://pubmed.ncbi.nlm.nih.gov/15646400/
https://doi.org/10.1074/jbc.274.16.10936
https://doi.org/10.1007/s00253-011-3557-z
https://doi.org/10.1038/nchembio.2044
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2789310/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3827094/
https://doi.org/10.3390/toxins12090568
https://pubmed.ncbi.nlm.nih.gov/29788125/
https://doi.org/10.1038/s42003-020-0941-1
https://doi.org/10.3390/toxins12080474
https://doi.org/10.1073/pnas.1916617117
https://doi.org/10.3389/fmicb.2020.01895

Images

https://www.storyblocks.com/video/stock/3d-rendered-video-with-bacteria-b8fdzhkjjzj7rz7wf7

https://commons.wikimedia.org/wiki/File:E_coli_at_10000x,_original.jpg
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 ].