Deadly Proteins Behind Mad Cow Disease Might Help Us Fight Superbugs
The next frontier of antibiotics might come from an unexpected place. Recent research identifies potential antibiotic candidates from inside prions—proteins capable of causing some of the deadliest brain infections ever known, such as mad cow disease.
Scientists at the University of Pennsylvania used artificial intelligence to rapidly search hundreds of prions and prion-like proteins for peptides with antibacterial activity. They found several dozen promising candidates, two of which have already shown results treating bacterial infections in mice.
The team’s findings establish “prion-related proteins as a productive source space for antibiotic discovery,” the scientists wrote in their paper, published late last week in the journal Nature Microbiology.
Good guy prions?
Prions are some of the strangest things around. They’re the misfolded form of a protein naturally found in the body. When a prion comes across its “normal” counterpart, it can somehow induce the latter to turn into a prion itself, almost like a zombie infection.
Classic prion disorders like mad cow disease and Creutzfeldt-Jakob disease are caused by the steady accumulation of one particular type of protein, aptly named the prion protein; these disorders are universally fatal. Some scientists have also argued that other neurodegenerative conditions, such as Alzheimer’s disease, are caused by other kinds of misfolded proteins that act in a similar way to prions.
According to the study researchers, there’s growing evidence that prions and prion-like proteins are more than just harbingers of death. Studies have found that the normal prion protein and the prion-like amyloid beta (one of the drivers of Alzheimer’s) can have antimicrobial activity, for instance. So the team decided to conduct a sweeping analysis looking for antimicrobial peptide fragments within these proteins.
The researchers had previously built an AI model intended to predict the antimicrobial activity of any given peptide fragment, named APEX 1.1. Then they let APEX scan through 19.3 million short peptide fragments found in 2,897 prion and prion-like proteins. They initially uncovered 1,179 candidates, which the team narrowed down to 75 that showed the most potential. Of these, 59 were able to inhibit the growth of at least one bacterial germ in the lab, including 42 that did so at low levels (important for dosing considerations).
Finally, the researchers tested two of the strongest candidates on the skin of mice infected with Acinetobacter baumannii, a common source of drug-resistant infections in people. The candidates appeared to be roughly as effective as polymyxin B, an existing antibiotic often used as a last resort drug for certain drug-resistant infections.
The researchers have coined these antibacterial fragments collected from prions as “prionins.”
The future of prionins
More research is obviously needed to verify whether the team’s prionins can actually work as hoped—and safely—in people. The researchers also note their findings don’t settle the open question as to whether prions or prion-like proteins naturally tackle bacterial infections in our body.
At the same time, they do argue their work provides a strong proof of concept that prionins identified through AI can be viable antibiotic candidates for further testing.
“For a long time, drug discovery has been limited not only by what we can test, but by where we choose to look,” said senior study author César de la Fuente, director of the Machine Biology Group at the University of Pennsylvania Perelman School of Medicine, in a statement from the university. “AI is changing that. It gives us a way to search the hidden layers of biology and ask whether molecules associated with one story—in this case, disease—may also carry another story with therapeutic potential.”
With any luck, the proteins known for causing the scariest diseases around could someday turn into our antibacterial allies.
#Deadly #Proteins #Mad #Cow #Disease #Fight #Superbugsantibiotic resistance,experimental drugs,prions
The next frontier of antibiotics might come from an unexpected place. Recent research identifies potential antibiotic candidates from inside prions—proteins capable of causing some of the deadliest brain infections ever known, such as mad cow disease.
Scientists at the University of Pennsylvania used artificial intelligence to rapidly search hundreds of prions and prion-like proteins for peptides with antibacterial activity. They found several dozen promising candidates, two of which have already shown results treating bacterial infections in mice.
The team’s findings establish “prion-related proteins as a productive source space for antibiotic discovery,” the scientists wrote in their paper, published late last week in the journal Nature Microbiology.
Good guy prions?
Prions are some of the strangest things around. They’re the misfolded form of a protein naturally found in the body. When a prion comes across its “normal” counterpart, it can somehow induce the latter to turn into a prion itself, almost like a zombie infection.
Classic prion disorders like mad cow disease and Creutzfeldt-Jakob disease are caused by the steady accumulation of one particular type of protein, aptly named the prion protein; these disorders are universally fatal. Some scientists have also argued that other neurodegenerative conditions, such as Alzheimer’s disease, are caused by other kinds of misfolded proteins that act in a similar way to prions.
According to the study researchers, there’s growing evidence that prions and prion-like proteins are more than just harbingers of death. Studies have found that the normal prion protein and the prion-like amyloid beta (one of the drivers of Alzheimer’s) can have antimicrobial activity, for instance. So the team decided to conduct a sweeping analysis looking for antimicrobial peptide fragments within these proteins.
The researchers had previously built an AI model intended to predict the antimicrobial activity of any given peptide fragment, named APEX 1.1. Then they let APEX scan through 19.3 million short peptide fragments found in 2,897 prion and prion-like proteins. They initially uncovered 1,179 candidates, which the team narrowed down to 75 that showed the most potential. Of these, 59 were able to inhibit the growth of at least one bacterial germ in the lab, including 42 that did so at low levels (important for dosing considerations).
Finally, the researchers tested two of the strongest candidates on the skin of mice infected with Acinetobacter baumannii, a common source of drug-resistant infections in people. The candidates appeared to be roughly as effective as polymyxin B, an existing antibiotic often used as a last resort drug for certain drug-resistant infections.
The researchers have coined these antibacterial fragments collected from prions as “prionins.”
The future of prionins
More research is obviously needed to verify whether the team’s prionins can actually work as hoped—and safely—in people. The researchers also note their findings don’t settle the open question as to whether prions or prion-like proteins naturally tackle bacterial infections in our body.
At the same time, they do argue their work provides a strong proof of concept that prionins identified through AI can be viable antibiotic candidates for further testing.
“For a long time, drug discovery has been limited not only by what we can test, but by where we choose to look,” said senior study author César de la Fuente, director of the Machine Biology Group at the University of Pennsylvania Perelman School of Medicine, in a statement from the university. “AI is changing that. It gives us a way to search the hidden layers of biology and ask whether molecules associated with one story—in this case, disease—may also carry another story with therapeutic potential.”
With any luck, the proteins known for causing the scariest diseases around could someday turn into our antibacterial allies.
![These Are the 12 Ikea Products the Company’s Design Chief Personally OwnsThe Svarva lamp can be twisted into different shapes.
Courtesy of Johan EjdemoPS Svarva Floor Lamp“Some stuff I did myself, like this one. The Svarva lamp we made with the design group Front for the PS 2009 collection. They were quite newly established and so we did an armchair and this lamp. The desire was to do a wooden turned lamp, but you should also be able to twist it, articulate it.”“I felt that that would be very difficult to do. Along with a colleague in lighting at the time, I went to Hungary to this factory that was producing lamps for us. It was all metal tubes that they were doing, so we were a little bit hesitant whether they should be able to solve this. But they made some mock-ups based on the designer drawings. So we went there to have a look, and it was standing there. It was this floor lamp, and also a table lamp where the wooden beads were going in a circle and then up, like a snake.”“What we didn’t know was that next to the lamp factory was this factory that was doing the turned wooden beads, the small individual pieces that we put together. None of us knew that. It was just pure serendipity. So they were turning these wooden beads, and the lamp factory was putting them on the metal tubes, just like on a necklace. They had very little to do, so they were happy to get the business.”A Sinka Cabinet resides in Ejdemo’s hallway.
Courtesy of Johan EjdemoPS Sinka Cabinet“I have another favorite from that PS 2009 collection, it’s in my hallway. The PS Sinka, with the small drawers with a wooden base. Sinka means “dovetail” in Swedish, so the name explaining that construction.”“But the problem we had with this one was the packaging volume was too big. So what we did was each drawer is slightly shallower. So four drawers stack into each other. And four more drawers stack. There’s a little bit of a stopper in the back when you push them in, so they stop evenly at the front. There’s also a hidden compartment behind the smallest drawer. Really good drawers for all this stuff that is just lying around and getting in the way. In the top one I have all my keys that I no longer know where they go.”PS Jonsberg Vases“I have this vase from the PS collection to hold the cables [on my Samsung Serif TV]. It was a set, the Jonsberg vases by Hella Jongerius. There were four of them in different ceramic techniques. I had all four, but the terracotta one broke, which was a pity.” [It certainly is. These vases now sell secondhand for ,700 for a full set.]“They’re inspired by different regions, and the different techniques are beautiful. I use the big black one for toilet paper in one bathroom. It’s not disrespect for the design. It’s just such a good design to stand there, and it makes the bathroom beautiful, and it can fit the toilet roll. So, why have something like an ugly stick? It’s nice for that.”Pax Wardrobes“Pax. We have to mention Pax. I have Pax wardrobes in a few rooms, but also I’m a little bit peculiar. Like in the kitchen, these veneer doors have been sanded and hand-painted by me, just to make them fit my house, in my space. I repaint them sometimes.”Chipped Spraka pepper mills.
Courtesy of Johan EjdemoSpraka Pepper Mills“I have these pepper mills. One for white pepper, one for black pepper. That was also in a PS collection. We did these with Marcus Arvonen. These pepper mills are beautiful, and these have been around for, like, 20 years as well. They are pretty tall. A smaller version came later on, but I like these.”“They have their chips, yes, but this just makes them nicer. It’s age. They’ve been around and are used every day. Everything has a little bit of imperfection. You can spend your whole life bothering about that, but there should be some imperfection in life. Fix it? Then something else needs fixing. It just moves. Leave it, be proud.”Where’s the Billy Bookcase or Kallax?“I don’t have a Billy in the house now. But there have been! Kallax? I have owned many. Brilliant piece. Really good for vinyl, because that’s the time they come from. I listen to a lot of vinyl.”#Ikea #Products #Companys #Design #Chief #Personally #Ownsikea,design,home,furniture,household,interviews](https://i2.wp.com/media.wired.com/photos/6a33ff12acc128b064d51d9c/master/w_1600%2Cc_limit/IKEA%2520PS%2520SVARVA%25202.jpg?ssl=1 "These Are the 12 Ikea Products the Company’s Design Chief Personally OwnsThe Svarva lamp can be twisted into different shapes.
Courtesy of Johan EjdemoPS Svarva Floor Lamp“Some stuff I did myself, like this one. The Svarva lamp we made with the design group Front for the PS 2009 collection. They were quite newly established and so we did an armchair and this lamp. The desire was to do a wooden turned lamp, but you should also be able to twist it, articulate it.”“I felt that that would be very difficult to do. Along with a colleague in lighting at the time, I went to Hungary to this factory that was producing lamps for us. It was all metal tubes that they were doing, so we were a little bit hesitant whether they should be able to solve this. But they made some mock-ups based on the designer drawings. So we went there to have a look, and it was standing there. It was this floor lamp, and also a table lamp where the wooden beads were going in a circle and then up, like a snake.”“What we didn’t know was that next to the lamp factory was this factory that was doing the turned wooden beads, the small individual pieces that we put together. None of us knew that. It was just pure serendipity. So they were turning these wooden beads, and the lamp factory was putting them on the metal tubes, just like on a necklace. They had very little to do, so they were happy to get the business.”A Sinka Cabinet resides in Ejdemo’s hallway.
Courtesy of Johan EjdemoPS Sinka Cabinet“I have another favorite from that PS 2009 collection, it’s in my hallway. The PS Sinka, with the small drawers with a wooden base. Sinka means “dovetail” in Swedish, so the name explaining that construction.”“But the problem we had with this one was the packaging volume was too big. So what we did was each drawer is slightly shallower. So four drawers stack into each other. And four more drawers stack. There’s a little bit of a stopper in the back when you push them in, so they stop evenly at the front. There’s also a hidden compartment behind the smallest drawer. Really good drawers for all this stuff that is just lying around and getting in the way. In the top one I have all my keys that I no longer know where they go.”PS Jonsberg Vases“I have this vase from the PS collection to hold the cables [on my Samsung Serif TV]. It was a set, the Jonsberg vases by Hella Jongerius. There were four of them in different ceramic techniques. I had all four, but the terracotta one broke, which was a pity.” [It certainly is. These vases now sell secondhand for ,700 for a full set.]“They’re inspired by different regions, and the different techniques are beautiful. I use the big black one for toilet paper in one bathroom. It’s not disrespect for the design. It’s just such a good design to stand there, and it makes the bathroom beautiful, and it can fit the toilet roll. So, why have something like an ugly stick? It’s nice for that.”Pax Wardrobes“Pax. We have to mention Pax. I have Pax wardrobes in a few rooms, but also I’m a little bit peculiar. Like in the kitchen, these veneer doors have been sanded and hand-painted by me, just to make them fit my house, in my space. I repaint them sometimes.”Chipped Spraka pepper mills.
Courtesy of Johan EjdemoSpraka Pepper Mills“I have these pepper mills. One for white pepper, one for black pepper. That was also in a PS collection. We did these with Marcus Arvonen. These pepper mills are beautiful, and these have been around for, like, 20 years as well. They are pretty tall. A smaller version came later on, but I like these.”“They have their chips, yes, but this just makes them nicer. It’s age. They’ve been around and are used every day. Everything has a little bit of imperfection. You can spend your whole life bothering about that, but there should be some imperfection in life. Fix it? Then something else needs fixing. It just moves. Leave it, be proud.”Where’s the Billy Bookcase or Kallax?“I don’t have a Billy in the house now. But there have been! Kallax? I have owned many. Brilliant piece. Really good for vinyl, because that’s the time they come from. I listen to a lot of vinyl.”#Ikea #Products #Companys #Design #Chief #Personally #Ownsikea,design,home,furniture,household,interviews")
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