Promises to revolutionize how drug discovery teams guide their studies
Biologists at the University of California, San Diego have developed a revolutionary new method for identifying and characterizing antibiotics, an advance that could lead to the discovery of new antibiotics to treat antibiotic resistant bacteria.
The researchers, who published their findings in this week’s early online edition of the journal Proceedings of the National Academy of Sciences, made their discovery by developing a way to perform the equivalent of an autopsy on bacterial cells.
“This will provide a powerful new tool for identifying compounds that kill bacteria and determining how they work,” said Joseph Pogliano, a professor of biology at UC San Diego who headed the research team. “Some bacteria have evolved resistance to every known class of antibiotic and, when these multi-drug resistant bacteria cause an infection, they are nearly impossible to treat. There is an urgent need for new antibiotics capable of treating infections caused by antibiotic resistant bacteria.”
The Centers for Disease Control and Prevention issued an alarming report in March that antibiotic-resistant strains of Carbapenem-Resistant Enterobacteriaceae, or CRE, had been found to cause infections in patients in nearly 200 hospitals in the United States alone. Because no antibiotics on the market are effective at treating these infections, about one-half of patients die from CRE infections. These outbreaks are difficult to contain, and in a 2011 outbreak of Klebsiella pneumonia at the U.S. National Institutes of Health Clinical Center, the bacteria spread despite strict infection control procedures and was detected in drains and medical devices that had been subject to standard decontamination protocols.
“We are finally running out of the miracle drugs,” said Pogliano, who detailed the history: The antibiotic penicillin was first discovered in the late 1920s, and received widespread clinical use in the 1940s. However, bacteria quickly evolved resistance to penicillin, so new and better versions were developed. Since that time, a continuous race has been fought to identify new antibiotics in order to stay one step ahead of the evolving resistance. In the 2011 outbreak of Klebsiella, the bacteria evolved resistance even to colistin, a drug of last resort because of its severe side effects.
Over the last 25 years, the number of new antibiotics entering the clinic has drastically declined. At the same time, bacteria have continued to evolve resistance to all of the currently available drugs, creating the current critical situation. One of the main problems in identifying new antibiotics and bringing them to market is a lack of understanding how the molecules work.
“It’s easy to identify thousands of molecules capable of killing bacteria,” explained Kit Pogliano, a professor of biology and a co-author of the paper. “The hard part is picking out the winners from the losers, and choosing molecules that are the best candidates for drug development. One key piece of information needed for this choice is knowledge of how the drug works, but this is traditionally difficult information to obtain, usually requiring months of intensive work. We’ve applied 21st century methods that within just two hours provide this information, allowing more rapid prioritization of new molecules. This will open up the discovery pipeline, allowing us to more rapidly identify new molecules with potential to enter the clinic for treatment of multi-drug-resistant pathogens.”
One key to this new approach was the combination of microscopy and quantitative biology tools. “We had to develop all of the cell biology and quantitative biology methods for generating the data ourselves and that required a lot of work, but now that we have the method working, it is very exciting,” said Poochit Nonejuie, a graduate student in the Division of Biological Sciences and another co-author. “My chemistry colleagues can give me a new molecule in the morning, and by the afternoon I can tell them the likely cellular pathways that they target. It’s mind blowing how powerful the technology is.”
The UC San Diego biologists say their new method is not only game changing, but promises to revolutionize how drug discovery teams guide their studies. With previous methods, understanding how an antibiotic works requires many different biochemical assays to be performed, which requires a lot of time and relatively large quantities of the compound, which is almost always in short supply when it is first discovered.
“Our new method represents the first time that a single test can be performed and identify the likely mechanism of action for a new compound,” said Joseph Pogliano. He noted that postdoctoral fellow Anne Lamsa has miniaturized the method so that it requires just a few nanograms of each drug candidate, conserving molecules that are often available only in tiny quantities.
The Latest Bing News on:
Drug discovery
- Major AlphaFold upgrade offers boost for drug discoveryon May 8, 2024 at 8:13 am
“We have to strike a balance between making sure that this is accessible and has the impact in the scientific community as well as not compromising Isomorphic’s ability to pursue commercial drug ...
- Google DeepMind’s Latest AI Model Is Poised to Revolutionize Drug Discoveryon May 8, 2024 at 7:59 am
R esearchers at Google DeepMind have developed AlphaFold 3, an AI model that can predict the structure of and interactions between biological molecules including proteins, DNA and ...
- VantAI Appoints John Cuozzo as Senior Vice President, Head of Drug Discoveryon May 8, 2024 at 7:24 am
VantAI, a leader in generative AI and drug discovery, today announced the appointment of John Cuozzo, PhD as SVP, Head of Drug Discovery. Cuozzo is an experienced scientific leader with a strong track ...
- Google DeepMind Unveils Next Generation of Drug Discovery AI Modelon May 8, 2024 at 4:03 am
The interactions of proteins - from enzymes crucial to the human metabolism, to the antibodies that fight infectious diseases - with other molecules is key to drug discovery and development. DeepMind ...
- DeepMind CEO Targets $100 Billion-Plus AI Drug Discovery Business With AlphaFoldon May 8, 2024 at 4:00 am
Isomorphic Labs, a unit of Alphabet Inc. created three years ago, was built to commercialize DeepMind’s AI for drug discovery. DeepMind first released AlphaFold in 2018, with advances in decoding the ...
- Generative AI Finds Its Footing in Drug Developmenton May 7, 2024 at 9:06 pm
Since the 2022 launch of ChatGPT, biopharma has poured money into this new form of artificial intelligence, but companies remain cautious with unproven technology.
- Open-Source AI Tool Streamlines Cancer Drug Candidate Generationon May 7, 2024 at 1:42 pm
Researchers at the University of California, San Diego have created a machine-learning system that mimics the laborious chemistry required in the initial stages of drug discovery.
- Model Medicines' AI-Driven Drug Discovery Delivers Groundbreaking Advances in New Chemistry and Biologyon May 7, 2024 at 3:13 am
From helping doctors answer patient questions to making new drugs to cure hard diseases, there has been a lot of hype about how artificial intelligence (AI) is going to improve human health. In this ...
- Kronos Bio: Underestimated Drug Discovery Platformon May 6, 2024 at 3:40 pm
Kronos Bio, Inc.'s drug discovery platform shows potential in targeting transcription regulatory networks. KRON has catalysts as soon as June, click for more.
- Researchers develop new AI tool for fast and precise tissue analysis to support drug discovery and diagnosticson May 6, 2024 at 9:16 am
A team of scientists from A*STAR's Genome Institute of Singapore (GIS) and Bioinformatics Institute (BII) has developed a new AI software tool called "BANKSY" that automatically recognizes the cell ...
The Latest Google Headlines on:
Drug discovery
[google_news title=”” keyword=”Drug discovery” num_posts=”10″ blurb_length=”0″ show_thumb=”left”]
The Latest Bing News on:
New antibiotics
- New plan to tackle antimicrobial resistance launchedon May 7, 2024 at 9:37 pm
A new plan to tackle antimicrobial resistance (AMR), a global issue that makes infections difficult or impossible to treat, has been launched today.
- A mother's loss launches a global effort to fight antibiotic resistanceon May 7, 2024 at 3:00 am
Diane Shader Smith's daughter, Mallory Smith, died at age 25 after fighting an antibiotic-resistant lung infection for 12 years. A new book of her daughter's diary entries and a website are aimed at ...
- Automated alerts improved antibiotic prescribing for common infections: JAMA studieson May 3, 2024 at 12:15 pm
Pneumonia and urinary tract infections are the two most common infections requiring hospitalizations and major reasons for the overuse of broad-spectrum antibiotics. | Algorithm-driven alerts help ...
- FDA Approves New Antibiotic for Uncomplicated Urinary Tract Infectionson April 30, 2024 at 11:30 pm
The U.S. Food and Drug Administration has approved Pivya (pivmecillinam) tablets for the treatment of female adults with uncomplicated urinary tract infections (UTIs). The approval is for UTIs caused ...
- Swedish-led team discovers potential new class of antibiotics, hope for AMR fighton April 29, 2024 at 11:22 am
A new antibiotic against gram-negative bacteria hasn’t been developed since the 1970s. Now, a European research team led by Swedish scientists has discovered multi-drug-resistant bug-killing compounds ...
- FDA Approves New Antibiotic for Uncomplicated UTIson April 26, 2024 at 11:54 am
The US Food and Drug Administration has approved pivmecillinam (Pivya) tablets to treat uncomplicated urinary tract infections in women.
- What to Know About Pivya, the New Antibiotic Treatment for UTIson April 26, 2024 at 4:06 am
The Food and Drug Administration recently approved Pivya (pivmecillinam) to treat uncomplicated UTIs in female adults. Clinical trials show that Pivya is effective and side effects are limited.
- Why Doctors Prescribe Older, Less Effective Antibiotics, When New, Less Toxic Treatments Save Liveson April 25, 2024 at 9:00 pm
According to a recent National Institutes of Health (NIH) report, doctors in the United States are still relying on older, less effective, toxic medicines to fight new, highly drug-resistant bacterial ...
- FDA Approves New Antibiotic Against UTIson April 25, 2024 at 7:40 am
So, it's welcome news that the U.S. Food and Drug Administration on Wednesday approved Pivya (pivmecillinam) to fight bacterial UTIs. "UTIs are a very common condition impacting women and one of the ...
- F.D.A. Approves Antibiotic for Increasingly Hard-to-Treat Urinary Tract Infectionson April 24, 2024 at 1:45 pm
Pivmecillinam, which has been used in Europe for decades, will become available next year to women 18 and older.
The Latest Google Headlines on:
New antibiotics
[google_news title=”” keyword=”new antibiotics” num_posts=”10″ blurb_length=”0″ show_thumb=”left”]