The news has been abuzz with excitement over Teixobactin, the first brand new antibiotic that has been discovered in decades. What's the truth behind the breathless headlines ? What should we really be excited about ?
Why all the fuss over a new antibiotic ?
It's been a very long time since a new viable antibiotic was discovered, which is a major problem because in the meantime bacteria have been busy evolving resistances to the few antibiotics that we do have. We now have to worry about bacteria which are resistant to all antibiotics. There are strains of Vibrio cholerae , Klebsiella pneumoniae and Escherichia coli which are resistant to pretty much everything we can throw at them. It's only a matter of time before other bacteria can become fully resistant.
We are lurching into the post antibiotic era, where germs once more emerge as the biggest cause of human suffering. Even the most minor surgery would become fraught with peril. Even the people who are lucky enough to be immune to such diseases could still be carriers, which could mean job losses for anyone working in catering and food production.
We desperately need new antibiotics. Teixobactin is such a big deal.
Where does Teixobactin come from ?
We'll get into this in much greater detail when I tell you how you can become a bioprospector, but basically it comes from a bacterium called Eleftheria terrae. It lives in the soil, which as you've probably heard is full of bacteria. What you may not have heard is that those bacteria are often in competition, killing each other for resources. It turns out that Eleftheria terrae's preferred weapon in this war is Teixobactin.
How does it work ?
Like all antibiotics, it's a poison that kills bacteria, and doesn't affect humans. It may shock you to know that there are some key differences between bacteria and humans.
Bacteria are different from humans ? How surprising !
I know, I know, I am the master of the obvious. I make this point, because Teixobactin exploits one of, if not the key difference between humans and bacteria.
We are made of millions of cells, each of whom has evolved to fulfill a specific role to ensure the survival of you. To the point where no single cell can survive on its own. Your skin cells defend the rest of your body from attack, but without the rest of the body to nourish them, those skin cells would die off on their own.
Bacteria on the other hand are single celled organisms. They're independent, and each cell is capable of surviving on it own. Their cells need to be tougher. Whilst our cells just have a soft malleable membrane, bacteria need something more. Which is why they enclose their cell membranes in a thick cell wall.
If you have a chemical that stops them making their cell wall properly, you can weaken and even kill them off. If you put that same chemical in a human cell, what's it going to do ? It can't stop human cells from making a cell wall that it doesn't have in the first place. It's as effective trying to kick a whales shins. Which is why antibiotics that attack the bacterial cell wall don't end up poisoning us.
The bacterial cell wall is central to the existence of many different species of bacteria. This is why Penicillin can kill off a huge range of different bacteria. Teixobactin also targets the cell wall, which means that it should also be able to kill off a range of different bacteria.
If Teixobactin is supposed to be lethal to ALL bacteria, how come it doesn't kill off the bacteria that makes it ?
The bacteria that makes it, Eleftheria terrae, protects its cell wall with an extra membrane. This membrane has chemical pumps which can help defend the cell wall against chemical attack. The thing is, Eleftheria terrae isn't the only bacterium which has this kind of cell membrane. There is a whole group of bacteria, called "gram negative"* which have this extra cell membrane.
It turns out that Teixobactin doesn't work against these types of bacteria at all. That extra cell membrane makes all the difference.
At least it should work against the fully resistant Vibrio Cholerae, right ?
That's a gram negative bacteria. No dice
Well , what about that fully resistant Klebsiella pneumoniae?
Also a gram negative bacteria. Sorry, won't work.
Does it work against any of these fully resistant strains?
Pretty much all of the really resistant bacteria are gram-negative. All of the bacteria that currently carry the New Delhi Metalloproteinase are gram negative. So Teixobactin isn't exactly going to save the world from the bacteria we're the most afraid of.
So what is it good for ?
It can kill the hell out of some of the more dangerous drug resistant bacteria. MRSA and it's more dangerous counterparts VRSA are vulnerable. It can destroy Clostridium difficile, and take out Tuberculosis. Even though it's not a miracle drug, it can still take out a bunch of dangerous diseases, which is good news.
They're saying this antibiotic is resistance proof, is it ?
People said the same thing about the Titanic. The truth was that the advertisements for the Titanic often had some qualifier "Designed to be unsinkable", or "practically unsinkable" rather than outright saying that "god himself could not sink this ship". But that PR clearly planted the idea of unsinkability in the general public. I think something similar has happened here.
There is a difference between "will never develop resistance" and "has not developed resistance" that the hype train seems to have missed.
One way to test whether bacterial resistance will evolve is through exposing bacteria to low levels of antibiotic, not enough to kill the bacteria, but enough to inconvenience them. Bacteria with mutations that help them survive better tend to thrive in this environment. So it's a good way of testing whether bacteria can quickly develop resistance. The good news is that using this test, no bacteria evolved resistance to Teixobactin. The bad news is that this test isn't full proof.
The authors themselves point out that this isn't the first time a drug has been found that produced negligible resistance. When Vancomycin was first discovered, resistance to it was thought to either evolve very slowly, or not at all. Guess what ? Vancomycin resistance has totally happened.
So why are people saying that this antibiotic is resistance proof ?
The basic theory goes like this. Since gram-negative bacteria have natural resistance to Teixobactin due to their extra cell membrane, bacteria without that specialised membrane can never become resistant to Teixobactin. So in theory, the only way for bacteria like MRSA to evolve resistance to Teixobactin is to drastically change their biology, and evolve that second membrane.
That theory assumes there is only way to evolve resistance to Teixobactin. There could be others, but we just don't know about them yet. Bacteria are versatile life forms, and in the word of my favourite fictional scientist -
So is this good news or bad news ?
The discovery of this antibiotic is definitely good news. Perhaps the most interesting thing about this discovery isn't so much what they discovered, but how they discovered it.
What's that supposed to mean ?
Historically, our best antibiotics have come from nature. A whole swath of antibiotics have been found in soil microbes.
The problem is that we haven't been very good at finding soil microbes. 99% of soil microbes can't be grown in the lab. The conventional methods we use kill them off. It's impossible to tell whether a microbe produces an antibiotic if it's dead before you even have the chance to look at it.
The researchers in this study figured out a way to keep more of these soil microbes alive long enough for them to be grown in the lab.
How did they do that ?
It's actually very simple. They grew these soil bacteria in the soil before they tried growing them in the lab.
Here is how we isolate bacteria in traditional microbiology :-
- Take a sample
- Dilute it down
- Smear it on the surface of a Petri dish filled with agar, and whatever nutrients we think those soil microbes, ideally replicating the nutrients they have in the soil
- Put it in an incubator
- Look at what grows.
They used a different strategy. I am simplifying a lot here, but this is what they did.
- Take a sample of soil
- Dilute the sample down
- Suspend the bacteria in agar
- Protect the agar with a semi permeable membrane
- Stick it back into the soil
- Let it grow under its natural conditions for a month
- Take it out, and see what's grown
The semi-permeable membrane prevents other soil microbes invading and contaminating the sample, but more importantly it allows for soil nutrients to seep in and nourish the sample bacterium. It uses the bacteria's own natural environment to help it to grow.
That's great, so can we now grow ALL THE SOIL BACTERIA ?
No, according to this study, at best only 50% of soil bacteria can be recovered this way. But on the plus side, that's way better than 1%. They only tested the soil samples from Maine. who knows what could be found if we looked further afield, in different soils.
That's why this paper is more important than just Teixobactin. Whether or not Teixobactin actually lives up to its own hype, this new method for discovering antibiotics could be the "Game Changer" we're looking for.
*They're called gram negative, because back in the long long ago, in the before time, bacteriologists used dyes to see bacteria. One of the most popular was crystal violet, otherwise known as "Gram's stain" after the guy who first used it on bacteria. The thing is, bacteria with an extra cell membrane resist this dye. They turn up negative on samples tested with gram's stain, hence making them "gram negative".
Concept art of Drix from Osmosis Jones, Sketch by Richard Bazley, check out more of his cool conept art at his website.
Gifs from Know your Meme and Reddit