Australian Researchers Unveil Revolutionary Method to Combat Drug-Resistant Bacteria
Australian scientists have developed a groundbreaking approach to tackle drug-resistant bacteria by creating antibodies that specifically target a sugar molecule unique to bacterial cells. This innovation has the potential to pave the way for a new generation of immunotherapies against multidrug-resistant hospital-acquired infections.
The research, published in Nature Chemical Biology, demonstrates that a laboratory-produced antibody can effectively combat a lethal bacterial infection in mice by homing in on a distinctive bacterial sugar and marking the pathogen for destruction by the immune system.
The study was led by Professor Richard Payne from the University of Sydney, in collaboration with Professor Ethan Goddard-Borger from WEHI and Associate Professor Nichollas Scott from the University of Melbourne and the Peter Doherty Institute for Infection and Immunity.
Professor Payne is also the director of the recently established Australian Research Council Centre of Excellence for Advanced Peptide and Protein Engineering, which aims to build on these discoveries to accelerate the translation of applications in biotechnology, agriculture, and conservation.
"This study showcases the potential of combining chemical synthesis with biochemistry, immunology, microbiology, and infection biology," said Professor Payne. "By precisely constructing these bacterial sugars in the lab using synthetic chemistry, we were able to understand their shape at the molecular level and develop antibodies that bind them with high specificity. This opens up new avenues for treating some devastating drug-resistant bacterial infections."
The target of the new antibody is pseudaminic acid, a sugar molecule that, while resembling sugars found on human cells, is exclusively produced by bacteria. Many dangerous pathogens use this sugar as an essential component of their outer coats to evade immune responses.
Since humans do not produce this sugar, it presents a highly differentiated target for immunotherapy development. To exploit this vulnerability, the team chemically synthesized the bacterial sugar and sugar-decorated peptides from scratch, allowing them to determine the exact three-dimensional arrangement of the molecule and its presentation on bacterial surfaces.
Using these insights and molecules, they developed a "pan-specific" antibody capable of recognizing the sugar across a wide range of bacterial species and strains.
In mouse infection models, the antibody successfully eliminated multidrug-resistant Acinetobacter baumannii, a notorious cause of hospital-acquired pneumonia and bloodstream infections. Multidrug-resistant Acinetobacter baumannii is a critical threat in modern healthcare facilities worldwide, often resisting even last-line antibiotics.
"Our work serves as a powerful proof-of-concept experiment that opens the door to the development of new life-saving passive immunotherapies," said Professor Goddard-Borger. "Passive immunotherapy involves administering ready-made antibodies to rapidly control an infection, rather than waiting for the individual's adaptive immune system to respond. This strategy can be used both therapeutically and prophylactically, which could be deployed to protect vulnerable patients in intensive care units."
Associate Professor Scott highlighted the antibodies' role in providing a powerful new tool for understanding how bacteria cause disease. "These sugars are central to bacterial virulence, but they've been very hard to study," he said. "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."
Over the next five years, the team aims to translate these findings into clinic-ready antibody therapies targeting multidrug-resistant A. baumannii. Success would effectively remove the 'A' from the ESKAPE pathogens, a significant milestone in the global fight against antimicrobial resistance.
"This is exactly the kind of breakthrough the new ARC Centre of Excellence is designed to enable," said Professor Payne. "Our goal is to turn fundamental molecular insight into real-world solutions that protect the most vulnerable people in our healthcare system."
Source:
Journal reference:
Tang, A. H., et al. (2026). Uncovering bacterial pseudaminylation with pan-specific antibody tools. Nature Chemical Biology. DOI:10.1038/s41589-025-02114-9. https://www.nature.com/articles/s41589-025-02114-9
