jouw wetenschapsgids in de hoofdstad

jouw wetenschapsgids in de hoofdstad

Saving the world from anthrax with … a llama

Antonella Fioravanti is a sharp young scientist, and the freshly announced winner of the prestigious ‘Eos Pipet 2020’ prize. Yes, she’s working for our alma mater VUB and VIB, so we might be a bit biased here at Wtnschp. So forget our favoritism and simply let her story convince you!

Let’s introduce you to Antonella’s object of rigorous study: Bacillus anthracis, the bacterium that causes anthrax disease. Bacteria are single-celled organisms. You can find them anywhere: from the bottom of the sea to the plants in your living room and not to shock you, but your own intestines are full of them as well! And while a lot of bacteria are good, some are bad. B. anthracis, unfortunately, is not our friend …

 

ANTHRAX BACTERIA ARE NOT YOUR FRIEND

Bacillus anthracis can go into a dormant, non-active state called a ‘spore’. Think of it as a sleeping beauty, but in this case, a dangerous one. It can survive for a very long time, even in extreme environments like hot or cold temperatures, high pressure and so on. It waits around innocently, until a new host comes along. That host could be a goat or a donkey that eats contaminated grass, or if you’re out of luck, even you can inhale a spore. If you inhale this sneaky bastard, chances are you’ll die. Once a spore reaches your intestines or your lungs, it grows into its active form and infects the body. It’s very effective and there’s no good cure available yet, so that explains why anthrax has been developed as a bioweapon by a number of countries.

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Anthrax bacteria can go into a dormant state, like a dangerous sleeping beauty, waiting ‘innocently’ for the next host to come along.

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Vindt u dat docenten de maatschappij meer moeten betrekken bij de opleiding, is daar groeiruimte in?

Wij proberen dat al met het BioMedical Science Centre Brussels en een initiatief als het Open BioLab, dat we openstellen voor iedereen. De kenniscentra van de Erasmushogeschool zijn er ook op gericht om in interactie te gaan met stakeholders, met de maatschappij. Het kenniscentrum mag nooit een entiteit op zich zijn, maar moet in wisselwerking blijven met de opleiding. Het zou voor mij een falen zijn als er niets terugvloeit naar de opleiding of als er geen studenten aan deelnemen. Wat wij proberen te doen, is research & development op vraag van eender wie, en dat kan op verschillende niveaus. Als de partners willen dat ik of iemand van het team met doctoraatservaring het doet, hangt daar een bepaald prijskaartje aan vast. Als studenten het project mogen en willen doen, kunnen wij moeilijk een resultaatsverbintenis aangaan, maar wel het engagement. Zo hebben we bijvoorbeeld in het kader van een vak klonering gedaan voor de VUB. De studenten vonden het leuk dat ze hadden meegewerkt aan iets dat daarna nog verder gebruikt wordt in wetenschappelijk onderzoek.

 

Interview: Catherine Morel – Uitwerking: Zoë Vanbiervliet & Floor Keersmaekers

But with or without the regrettable meddling of humanity, anthrax is a force to be reckoned with. And it’s been around for a while. Traces of spores were found in mammoths and Egyptian mummies, and we’re pretty sure the 5th plague that the bible is talking about was actually anthrax. For a long time, people didn’t understand what was going on. When livestock perished in droves, they called it ‘a plague’ or thought the fields were simply ‘cursed’.

mummy egypt (Image by albertr from Pixabay)

We’ve been able to pin this enemy down as a harmful bacterium since more than a century, but there is still no proper way to fight it. It keeps popping up, like in the anthrax outburst of 2016 in Siberian reindeer. Contaminated ground that had been frozen for eternity, melted because of climate change that caused an increase of temperature in this area. Because anthrax spores can survive these extremely icy conditions, new contaminated grass grew, was eaten by the poor reindeer et voilà, a new 5th plague is never far away. Not to mention of course that millions of people have been killed by anthrax by human hand. Let’s all agree, it’s more than scary.

WHAT DOES THE ENEMY LOOK LIKE?

Okay, I think we’ve made it more than clear that anthrax is no joke, and worth to fight. Let’s take a closer look.

All bacteria have a membrane on the outside, you could call it their skin. But some of them, including Bacillus anthracis, have an ‘extra’ layer around them: the mighty S-layer. Since the bacteria are investing 10 to 15% of their energy in making it, it must be important to them, right?

Vindt u dat docenten de maatschappij meer moeten betrekken bij de opleiding, is daar groeiruimte in?

Wij proberen dat al met het BioMedical Science Centre Brussels en een initiatief als het Open BioLab, dat we openstellen voor iedereen. De kenniscentra van de Erasmushogeschool zijn er ook op gericht om in interactie te gaan met stakeholders, met de maatschappij. Het kenniscentrum mag nooit een entiteit op zich zijn, maar moet in wisselwerking blijven met de opleiding. Het zou voor mij een falen zijn als er niets terugvloeit naar de opleiding of als er geen studenten aan deelnemen. Wat wij proberen te doen, is research & development op vraag van eender wie, en dat kan op verschillende niveaus. Als de partners willen dat ik of iemand van het team met doctoraatservaring het doet, hangt daar een bepaald prijskaartje aan vast. Als studenten het project mogen en willen doen, kunnen wij moeilijk een resultaatsverbintenis aangaan, maar wel het engagement. Zo hebben we bijvoorbeeld in het kader van een vak klonering gedaan voor de VUB. De studenten vonden het leuk dat ze hadden meegewerkt aan iets dat daarna nog verder gebruikt wordt in wetenschappelijk onderzoek.

 

Interview: Catherine Morel – Uitwerking: Zoë Vanbiervliet & Floor Keersmaekers

Wall piece (Part of image by Pezibear from Pixabay)

Why mighty? First of all, the S-layer is super strong, like an armor. Secondly, it self assembles! It’s made up of tiny pieces (proteins), that automatically assemble into a layer. Imagine a pile of bricks automatically forming a wall. It sounds like a superpower, but it’s true.

The problem with this mighty S-layer is that it’s so strong, nobody succeeded in breaking it down. That is, until Antonella came along and tore the armor to bits. That might sound easy, but is pretty impressive if you know that it has seemed unbreakable since its discovery in the 50’s!   

AND THEN CAME ANTONELLA

To destroy this mighty ‘S-wall’, she and her team first had to figure out what a single ‘brick’ or protein in the S-layer looked like. By applying x-ray crystallography, she was able to uncover the atomic structure of the protein. Now that she had the blueprint figured out, she could produce and study as many copies of the ‘bricks’ in her lab as she wanted.

Sap protein (Fioravanti et al. 2019; Nature Microbiology)

The protein’s structure (Fioravanti et al. 2019; Nature Microbiology)

The next step was to find something that could target these proteins and block their normal behavior. One way to do that is to let our immune system do its work.

If an ‘outside enemy’ enters our body, our immune system kicks in and instantly starts making ‘antibodies’. These antibodies are able to recognize and neutralize the new enemy. Think of it as police officers with handcuffs of the perfect size and shape to ‘capture’ the enemy. It won’t surprise you that these neutralizing handcuffs are exactly what Antonella had in mind!

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Antibodies can neutralize a new enemy. Like police officers with handcuffs of the perfect size and shape to ‘capture’ them.

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LAMA TO THE RESCUE

This is already pretty interesting, but even more astonishing is what happens in animals like camels, sharks and … llamas! When you present them a new enemy, their immune system makes super tiny police officers. Imagine that. The big advantage is that in the lab, they let go of their handcuffs more easily, and the handcuffs still work like a charm without their officer. They’re small, stable and easier to recreate in a lab. Scientists call these amazing llama handcuffs ‘nanobodies’.

Still with us? So far, we’ve got an enemy (the ‘bricks’ or proteins in the S-layer) and an idea to neutralize them (with the ‘handcuffs’ or llama nanobodies).

So, Antonella’s genius plan was to introduce her S-layer proteins to a llama. The immune system of the llama would then do its job and produce ‘nanobodies’ that could neutralize these proteins. Not an easy job, but after ‘six weeks of madness’ as Antonella calls it, it worked! Her new woolly friend had produced a number of different nanobodies. After another six months of lab work, she had properly found and identified the nanobodies that did the trick.

Llama peeps over wall (Image by Pezibear from Pixabay)

The beautiful thing is that they neutralized the proteins exactly in the right spot. That is, the spot they normally use to glue together and form the ‘S-wall’. The nanobodies work so well that they’re not only capable of preventing the armor to form, they can even destroy the armor when it’s already there. That means, if you take a bunch of anthrax bacteria and bombard them with these special llama nanobodies, their once mighty armor shrinks, they’re not able to grow anymore and finally die.

Nbs effect on S-layer (Fioravanti et al. 2019; Nature Microbiology)

Scanning electron microscopy images of Bacillus anthracisCompare the healthy bacteria (left) with bacteria damaged by the nanobodies (right). You can clearly see the shrunken armor. (Image courtesy of Antonella Fioravanti and Han Remaut, VIB-VUB Center for Structural Biology)

 

Antonella succeeded to do this, not only with bacteria in the lab (in vitro), but during animal infection (in vivo) as well.

Mission accomplished. Armor destroyed. Anthrax slayed.

That’s where Antonella’s heroic science story ends for now, or even better, begins. After her publication in Nature Microbiology (FYI, check out her blog over there), she’s now reaching for the stars. She’s working on turning her initial success into a real therapy for anthrax, and she is already looking out for the next unwelcome bacteria to slay. Wtnschp wishes her all the best.

Antonella Fioravanti by Piotr Kolata

profile picture by Piotr Kolata

Dr. Antonella Fioravanti is a European scientist that obtained her master’s degree in Medical Biotechnology at the University of Florence (Italy) in 2010. She then joined the Laboratory of Comparative systems biology of signal transduction (Dr. Biondi, Lille CNRS-France) where in 2014 she obtained her PhD in Cellular and Molecular aspects of biology, performing breakthrough work on the role of epigenetic regulatory mechanisms in bacterial asymmetrical cell division.  Since October 2014 she joined the Structural and Molecular Microbiology group at VIB – Vrije Universiteit Brussel, headed by Professor Han Remaut. Here she had the opportunity to take over and lead the S-layer research project, with the aim of filling the gap in the structural and functional understanding of the bacterial Surface layers (S-layers) in the highly pathogenic bacterium Bacillus anthracis.

She currently spearheads the development of anti-layer assembly inhibitors as promising new tools to fight anthrax and other diseases caused by S-layer carrying pathogens.

photo on top: © Shutterstock
photos in article:
© Pixabay (mummy by albertr, llama and wall by Pezibear)