Researchers have discovered a powerful new antibiotic that uses a unique method to kill many types of drug-resistant bacteria, including the deadly hospital-acquired infection methicillin-resistant Staphylococcus aureus (MRSA). Scientists say this new compound provides hope in the arms race against antibiotic-resistant superbugs.
New Antibiotic Uses Novel Mechanism That Bacteria Cannot Easily Resist
The new antibiotic, named zosurabalpin, operates in a way that bacteria will find difficult to develop resistance against (PMLive, BBC News). Most antibiotics work by either blocking processes that are vital for bacterial growth, or destroying bacterial cell walls and membranes. Bacteria can evolve to overcome these antibiotics by altering the molecules targeted by the drugs.
Zosurabalpin instead works by binding to an important bacterial protein called BamA and triggering it to open a hole in the bacterial membrane that leads to cell death (Nature, PMLive). BamA is essential for building the outer membrane of certain bacteria, and these bacteria cannot alter the protein’s structure without compromising the membrane’s integrity.
“It’s very hard for bacteria to reshuffle that protein because it’s so fundamental to their survival,” said study co-author Kim Lewis of Northeastern University (Nature, New Scientist). “That makes zosurabalpin very durable as an antibiotic. Bacteria will find it very difficult to develop resistance.”
Early tests showed no signs that bacteria can gain resistance against even low concentrations of zosurabalpin (PMLive). “This gives me hope that antibiotics can make a comeback,” said University of North Carolina microbiologist Elizbeth Shank (BBC News).
Promising Results Against Deadly Superbugs In Early Trials
In lab tests, zosurabalpin effectively killed many types of Gram-negative bacteria, including species resistant to multiple classes of existing antibiotics (New Scientist). Gram-negative bacteria have an outer membrane that makes it harder for antibiotics to penetrate and reach their targets.
Zosurabalpin was tested against over 100 bacterial strains and found to inhibit the growth of all Acinetobacter baumannii samples, a dangerous superbug that has evolved resistance to nearly all available antibiotics (FierceBiotech, Securiites.io). The antibiotic also killed samples of carbapenem-resistant Enterobacterales (CRE), another multidrug-resistant Gram-negative bacterium that causes difficult-to-treat bloodstream infections (ABC News).
In studies with mice, zosurabalpin cured 90-100% of animals infected with drug-resistant forms of A. baumannii, Escherichia coli, and Klebsiella pneumoniae (Amp.TheGuardian). These deadly bacteria frequently spread in hospitals and cause pneumonia, sepsis, and meningitis that are extremely difficult to treat with existing medicines.
“Seeing the antibiotic successfully treat infected mice, including strains resistant to other antibiotics, was very exciting,” said University of Pittsburgh microbiologist Carey-Ann Burnham, who was not involved in the research (KTLA). “This suggests zosurabalpin could be very helpful for clearing stubborn bacterial infections in a clinical setting.”
New Approach To Antibiotic Discovery Using AI and High-Throughput Screening
Zosurabalpin was discovered using an innovative combination of artificial intelligence algorithms and rapid chemical screening techniques (Euronews). Researchers from MIT first used AI to analyze the molecular structures of over 2,500 compounds with some antibacterial activity. The AI identified shared features that contributed to a compound’s ability to kill bacteria or inhibit their growth.
| Compound Class | Key Antibacterial Features Identified by AI |
|---|---|
| Macrocycles | Constrained ring structures that can bind target proteins |
| Ruthenium complexes | Capable of generating reactive oxygen species |
| Acyldepsipeptides | Disrupt bacterial membranes |
The researchers then generated a library of over 100 million new drug candidates containing these beneficial chemical groups. They used high-throughput screening approaches to quickly test the large pool of compounds against bacteria and measure their antibacterial potency and toxicity (PMLive).
This novel methodology discovered 27 promising new antibiotics, including zosurabalpin – the first new class of antibiotics identified in over 60 years (Euronews). Experts say combining AI prediction models with rapid large-scale testing provides an efficient new paradigm for overcoming the innovation crisis in antibiotic development (Aids Health).
“AI can analyze data and spot patterns that humans cannot see. This allows more informed and rapid searching through vast chemical spaces,” said pharmaceutical chemist Madeline Lawson of Imperial College London, who was not part of the research group (PMLive). “Combined with high throughput assays, this technology could reinvigorate the slowing antibiotic pipeline.”
Calls To Incentivize New Antibiotic Development As Resistance Grows
The discovery of zosurabalpin and related compounds provides hope in the ongoing battle against the rising threat of antibiotic resistance (ResearchProfessionalNews). Bacteria are evolving resistance faster than new drugs are being developed, causing infections that are increasingly untreatable with available medicines. It is estimated that by 2050, antibiotic-resistant superbugs could kill up to 10 million people per year worldwide – more than cancer (Independent).
Many pharmaceutical companies have withdrawn from antibiotic research in recent years due to low profitability compared to drugs that treat chronic conditions (AidsHealth). But health experts say new incentives are urgently needed to drive innovation of new antimicrobials before untreatable superbugs become widespread (ResearchProfessionalNews, AidsHealth).
Proposed incentives include increased government funding for academic antibiotic programs, incentives for appropriate use of new antibiotics to slow resistance, and reimbursement models that provide reasonable profits from short-term treatments (AidsHealth, FierceBiotech).
“The rapid global spread of antibiotic resistance is outrunning new drug development,” warns microbiologist Lance Price of the Antibiotic Resistance Action Center (BBC News). “Discovering new classes of antibiotics should be an urgent public health priority before we lose the capability to treat deadly bacterial diseases that we have relied on for over a century.”
What This Means For The Future Fight Against Drug-Resistant Bacteria
Researchers say the unusual mechanism of zosurabalpin provides longevity against evolved antibiotic resistance, and its potency against Gram-negative superbugs fills an urgent need for new treatments (EnterpriseAI). Roche Pharmaceuticals has licensed rights to the antibiotic and expedited clinical trials in patients are expected to begin in 2025 after completing preclinical development and safety studies (Roche, FierceBiotech).
Scientists also think this new AI-assisted high-throughput screening technology can accelerate discovery of other promising antibiotic drug candidates with durable activity (KTLA). Several other novel compounds with different bacterial targets identified by the AI algorithms have strong potential as next-generation antibiotics. By continuing to expand chemical libraries and prediction models, researchers hope this methodology could provide a steady supply of new medicines to battle evolving antibiotic resistance (Tickernews, NewAtlas).
“This groundbreaking work underscores the power of artificial intelligence for new antibiotic discovery,” concludes infectious disease specialist Dr. Susan Davis of Ontario Public Health (National Post). “Finally we have a promising new technique to get ahead of dangerous bacteria and produce antibiotics we desperately need for emerging superbugs in the 21st century.”
To err is human, but AI does it too. Whilst factual data is used in the production of these articles, the content is written entirely by AI. Double check any facts you intend to rely on with another source.
