ChatGPT-like AI Creates New Bacteria-Killing Proteins

Using an AI model similar to the one powering internet darling ChatGPT, the California-based biotech Profluent has created novel antimicrobial proteins, and they’ve already proven capable of killing bacteria in the lab.

The successful proteins, published in Nature Biotechnology, were part of the first clutch of designs generated by Profluent’s AI platform, ProGen.

ProGen is a large language model (LLM), a form of Deep Learning AI that utilizes a universe’s worth of text as its training data, developing the ability to analyze and generate language — like ChatGPT, except in Progen’s case the language is that of proteins.

While companies are experimenting with exciting new biotechnology like CRISPR genome editing by repurposing what nature has given us, we’re doing something different,” Ali Madani, Profluent’s founder, said in a statement announcing the startups’ launch.

We use AI and large language models like the ones which power ChatGPT to learn the fundamental language of biology, and design new proteins which have the potential to cure diseases.

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Regenerative Therapy Reverses Hearing Loss

The biotechnology company Frequency Therapeutics is seeking to reverse hearing lossnot with hearing aids or implants, but with a new kind of regenerative therapy. The company uses small molecules to program progenitor cells, a descendant of stem cells in the inner ear, to create the tiny hair cells that allow us to hearHair cells die off when exposed to loud noises or drugs including certain chemotherapies and antibiotics. Frequency’s drug candidate is designed to be injected into the ear to regenerate these cells within the cochlea. In clinical trials, the company has already improved people’s hearing as measured by tests of speech perception—the ability to understand speech and recognize words.

Speech perception is the No. 1 goal for improving hearing and the No. 1 need we hear from patients,” says Frequency co-founder and Chief Scientific Officer Chris Loose Ph.D.

In Frequency’s first clinical study, the company saw statistically significant improvements in speech perception in some participants after a single injection, with some responses lasting nearly two years. The company has dosed more than 200 patients to date and has seen clinically meaningful improvements in speech perception in three separate clinical studies, with some improvements lasting nearly two years after a single injection. Another study failed to show improvements in hearing compared to the placebo group, but the company attributes that result to flaws in the design of the trial. Now Frequency is recruiting for a 124-person trial from which preliminary results should be available early next year.

The company’s founders, including Loose, MIT Institute Professor Robert Langer, CEO David Lucchino MBA, Senior Vice President Will McLean Ph.D., and Harvard-MIT Health Sciences and Technology affiliate faculty member Jeff Karp, are already gratified to have been able to help people improve their hearing through the clinical trials. They also believe they’re making important contributions toward solving a problem that impacts more than 40 million people in the U.S. and hundreds of millions more around the world.

Hearing is such an important sense; it connects people to their community and cultivates a sense of identity,” says Karp, who is also a professor of anesthesia at Brigham and Women’s Hospital. “I think the potential to restore hearing will have enormous impact on society.

Source: https://www.frequencytx.com/
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https://neurosciencenews.com/

Cannabis Ingredient to kill meningitis and pneumonia

Cannabidiol (CBD), the main nonpsychoactive ingredient of the cannabis plant, can kill Gram-positive bacteria and, more impressively, Gram-negative bacteria, which excel at antibiotic resistance because they enjoy an extra layer of protection, an outer cell membrane. The ability of CBD to slay Gram-negative bacteria is a new finding, one reported by a team of scientists in Australia. According to the scientists, CBD analogs could constitute the first new class of antibiotics against Gram-negative bacteria that has been developed since the 1960s.

The new finding appeared in the journal Communications Biology, in an article titled, “The antimicrobial potential of cannabidiol.” According to this article, CBD not only killed Gram-positive bacteria such as highly resistant Staphylococcus aureus, Streptococcus pneumoniae, and Clostridioides difficile, it also showed potency against the Gram-negative bacteria Neisseria gonorrhoeae, Neisseria meningitides, Moraxella catarrhalis, and Legionella pneumophila. These Gram-negative bacteria are responsible for sexually transmitted gonorrhea, life-threatening meningitis, airway infections (such as bronchitis and pneumonia), and Legionnaires’ disease, respectively.

Our results demonstrate that cannabidiol has excellent activity against biofilms, little propensity to induce resistance, and topical in vivo efficacy,” the authors of the article wrote. “Multiple mode-of-action studies point to membrane disruption as cannabidiol’s primary mechanism.”

The authors included scientists from the University of Queensland in Australia and Botanix Pharmaceuticals. At the University of Queensland’s Centre for Superbug Solutions, scientists led by associate professor Mark Blaskovich, PhD, mimicked a two-week patient treatment in laboratory models to see how fast the bacteria mutated to try to outwit CBD’s killing power.

Cannabidiol showed a low tendency to cause resistance in bacteria even when we sped up potential development by increasing concentrations of the antibiotic during ‘treatment,’” said Blaskovich, the corresponding author of the article in Communications Biology. “We think that cannabidiol kills bacteria by bursting their outer cell membranes, but we don’t know yet exactly how it does that, and we need to do further research.

Source: https://www.genengnews.com/

France Experiments Anti-Malarial And Antibiotic Combo To Fight COVID-19

A new study whose results were published in the International Journal of Antimicrobial Agents has found early evidence that the combination of hydroxychloroquine, a popular anti-malaria drug known under the trade name Plaqenuil, and antibiotic azithromycin (aka Zithromax or Azithrocin) could be especially effective in treating the COVID-19 coronavirus and reducing the duration of the virus in patients.

The researchers performed a study on 30 confirmed COVID-19 patients, treating each with either hydroxychloroquine on its own, a combination of the medicine with the antibiotic, as well as a control group that received neither. The study was conducted after reports from treatment of Chinese patients indicated that this particular combo had efficacy in shortening the duration of infection in patients.

20 of the 30 participants in the study received treatment, and the results showed that while hydroxycholoroquine was effective on its own as a treatment, when combined with azithromycin it was even more effective, and by a significant margin.

Since yesterday, tests have been conducted on a large scale through Europe in the hope to validate the first results.

Source: https://techcrunch.com/

How To Reengineer Viruses To Cure Bacterial Infections

The world is in the midst of a global “superbug crisis. Antibiotic resistance has been found in numerous common bacterial infections, including tuberculosis, gonorrhoea and salmonellosis, making them difficult – if not impossibleto treat. We’re on the cusp of a post-antibiotic era, where there are fewer treatment options for such antibiotic-resistant strains. Given estimates that antibiotic resistance will cause 10 million deaths a year by 2050, finding new methods for treating harmful infections is essential.

Strange as it might sound, viruses might be one possible alternative to antibiotics for treating bacterial infections. Bacteriophages (also known as phages) are viruses that infect bacteria.

They’re estimated to be the most abundant organisms on Earth, with probably more than 1031 bacteriophages on the planet. They can survive in many environments, including deep sea trenches and the human gut. While phages are efficient killers of bacteria, they don’t infect human cells and are harmless to humans.

Although phage therapy was used in the 1930s, it has since become a forgotten cure in the west. Although the treatment became commonplace in the former Soviet Union, it wasn’t adopted by western countries largely because of the discovery of antibiotics, which became widespread after World War II.

Bacteriophages are effective against bacteria because they’re able to attach themselves to the cell if they recognise specific molecules called receptors. This is the first step in the “infection” process. After attaching to the bacterial cell, the phage then injects its DNA inside the bacteria.

This causes one of two things to happen. After being injected with the phage’s DNA, the virus will take over the bacterial cell’s replication mechanism and start producing more phages. This process is known as a “lytic infection”. This disintegrates the cell, allowing the newly produced viruses to leave the host cell to infect other bacterial cells.

But sometimes, the phage DNA gets incorporated into the bacterial host’s chromosome instead, becoming a “prophage. It usually remains dormant but environmental factors, such as UV radiation or the presence of certain chemicals such as those found in sunscreen, can cause the phage to “wake up”, start a lytic infection, take over the host cell and destroy it.

Lytic bacteriophages are preferred for treatment because they don’t integrate into the bacterial host’s chromosome. But it’s not always possible to develop lytic bacteriophages that can be used against all types of bacteria. As each type of phage is only able to infect specific types of bacteria, they can’t infect a bacterial cell unless the bacteriophage can find specific receptors on the bacterial cell surface.

However, engineering techniques can remove the bacteriophage’s ability to integrate into the host’s genome, making them useful for treatment. Engineered phages have even successfully treated a drug-resistant Mycobacterium abscessus infection in a 15-year-old girl.

Source: https://www.realclearscience.com/

Deadly ‘SuperBugs’ Destroyed by Molecular Drills

Molecular drills have gained the ability to target and destroy deadly bacteria that have evolved resistance to nearly all antibiotics. In some cases, the drills make the antibiotics effective once again.

Researchers at Rice University, Texas A&M University, Biola University and Durham (U.K.) University showed that motorized molecules developed in the Rice lab of chemist James Tour are effective at killing antibiotic-resistant microbes within minutes.

These superbugs could kill 10 million people a year by 2050, way overtaking cancer,” Tour said. “These are nightmare bacteria; they don’t respond to anything.”

The motors target the bacteria and, once activated with light, burrow through their exteriors.

While bacteria can evolve to resist antibiotics by locking the antibiotics out, the bacteria have no defense against molecular drills. Antibiotics able to get through openings made by the drills are once again lethal to the bacteria.

Tour and Robert Pal, a Royal Society University Research Fellow at Durham and co-author of the new paper, introduced the molecular drills for boring through cells in 2017. The drills are paddlelike molecules that can be prompted to spin at 3 million rotations per second when activated with light.

Tests by the Texas A&M lab of lead scientist Jeffrey Cirillo and former Rice researcher Richard Gunasekera, now at Biola, effectively killed Klebsiella pneumoniae within minutes. Microscopic images of targeted bacteria showed where motors had drilled through cell walls.

Bacteria don’t just have a lipid bilayer,” Tour said. “They have two bilayers and proteins with sugars that interlink them, so things don’t normally get through these very robust cell walls. That’s why these bacteria are so hard to kill. But they have no way to defend against a machine like these molecular drills, since this is a mechanical action and not a chemical effect.”

The motors also increased the susceptibility of K. pneumonia to meropenem, an antibacterial drug to which the bacteria had developed resistance. “Sometimes, when the bacteria figures out a drug, it doesn’t let it in,” Tour said. “Other times, bacteria defeat the drug by letting it in and deactivating it.

He said meropenem is an example of the former. “Now we can get it through the cell wall,” Tour said. “This can breathe new life into ineffective antibiotics by using them in combination with the molecular drills.”

The researchers reported their results in the American Chemical Society journal ACS Nano.

Source: https://news.rice.edu/

How To Provoke Bacterial Suicide to Fight Antibiotic Resistance

Overuse of antibiotics has escalated the emergence of antibiotic-resistant bacteria. Unfortunately, the growth of resistance has outpaced the development and discovery of new antibiotics and limited the treatment of bacterial infections.

Now, scientists are turning to a uniquely human advantage, the ability to think and reason, to solve the issue. Now, we’re tricking pathogenic microbes into killing themselves.

In April, a team of French scientists published a new kind of molecular trickery that selectively kills harmful and antibiotic-resistant bacteria without traditional antibiotics. The research, led by genomicist Rocío López-Igual and colleagues at the Pasteur Institute capitalized on mechanisms of gene regulation to trick Vibrio cholerae into producing self-destructive toxins. This approach could be adapted to target other microbes and reduce the need for antibiotics.

Antibiotic-resistant bacteria are a major threat to human health

V. cholerae, which causes cholera, encodes multiple toxins in its genome. Bacterial toxins inhibit vital processes like DNA replication or cell division. Typically, anti-toxins – that the bacteria also produce themselves –protect bacteria from poisoning themselves. Stress activates the toxins, often leading to cell death. Although exactly why bacteria maintain deadly toxin genes is still puzzling, we know that artificially activating the toxins provides a route to kill bacteria. The star of López-Igual and her colleagues’ method is a toxin that inhibits, an important bacterial enzyme. Normally, DNA gyrase relieves stress from twisted DNA strands, so preventing DNA gyrase activity causes breaks in DNA. And like in human cells, such severe DNA damage is also fatal to bacterial cells.The researchers manipulated the DNA sequences of V. cholerae to create a code for production of the toxin in specific kinds of bacteria. The specificity of bacterial gene regulation ensures that only certain bacteria can interpret this code. Bad news for the ones that can: they end up triggering their own death.

Source: https://massivesci.com/