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  • 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 thatin 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. colithat 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 TAsystems. 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 usthanks 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 whicheventually, 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 perfectand since DNA is so small,  

  • they can't really see if it's workedwhich is  why the toxic gene is there in the first place.  

  • They know that only bacteria that have the wholecorrect 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 antibioticsthe 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 “decoytoxin to distract their antitoxinsallowing 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 ]

This episode is brought to you by  the Music for Scientists album,

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Why Bacteria Don't Outweigh the Earth

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    joey joey posted on 2021/07/01
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