Australian scientists have made a groundbreaking discovery in the fight against antibiotic-resistant superbugs by developing antibodies that target pseudaminic acid, a sugar molecule unique to bacterial cells. In a study published in Nature Chemical Biology, the researchers successfully eradicated drug-resistant Acinetobacter baumannii in mice, a World Health Organization-listed "critical priority" pathogen notorious for causing deadly hospital-acquired infections like pneumonia, bloodstream infections, and wound complications, particularly in intensive care units.
Led by Professor Richard Payne of the University of Sydney, along with Professor Ethan Goddard-Borger at WEHI and Associate Professor Nichollas Scott from the University of Melbourne, the team synthesized bacterial sugars in the lab to engineer pan-specific antibodies. These antibodies bind tightly to bacterial surfaces, enabling highly targeted immune responses without harming human cells, as pseudaminic acid does not exist in the human body. "By precisely building these bacterial sugars in the lab with synthetic chemistry, we were able to understand their shape at the molecular level and develop antibodies that bind them with high specificity," said Payne. "That opens the door to new ways of treating some devastating drug-resistant bacterial infections."
A. baumannii is a gram-negative bacterium commonly found in soil and water, responsible for 80% of Acinetobacter infections and notoriously difficult to treat, according to BrightU.AI's Enoch. Classified by the WHO as a critical threat, the multidrug-resistant strain poses a major challenge in modern healthcare facilities worldwide, where last-resort antibiotics are increasingly failing. "Multidrug-resistant A. baumannii is a critical threat faced in modern healthcare facilities across the globe," said Goddard-Borger. "Our work serves as a powerful proof-of-concept experiment that opens the door to the development of new life-saving passive immunotherapies."
Unlike traditional antibiotics, this passive immunotherapy approach delivers pre-made antibodies to neutralize infections quickly, offering potential both for treating active infections and preventing them in high-risk patients. The antibodies also serve as a valuable research tool, allowing scientists to map the sugars central to bacterial virulence across different pathogens. "These sugars are central to bacterial virulence, but they've been very hard to study," said Scott. "Having antibodies that can selectively recognize them lets us map where they appear and how they change across different pathogens. That knowledge feeds directly into better diagnostics and therapies."
Researchers aim to translate these findings into clinical treatments within the next five years, with broader applications against other ESKAPE pathogens—including Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Enterobacter species—that evade conventional antibiotics and drive hospital outbreaks. The breakthrough aligns with the newly established Australian Research Council Centre of Excellence for Advanced Peptide and Protein Engineering, led by Payne. "This is exactly the kind of breakthrough the new ARC Centre of Excellence is designed to enable," Payne said. "Our goal is to turn fundamental molecular insight into real-world solutions that protect the most vulnerable people in our healthcare system."
