Researchers in Australia have developed a promising new strategy to combat deadly bacteria that no longer respond to antibiotics. The team engineered antibodies that lock onto a sugar found only on bacterial cells, an approach that could support a new generation of immunotherapies for multidrug resistant infections acquired in hospitals.
The study, published in Nature Chemical Biology, shows that an antibody created in the laboratory was able to eliminate a normally fatal bacterial infection in mice. It works by binding to a distinctive bacterial sugar and alerting the immune system to destroy the invading pathogen.
The project was co led by Professor Richard Payne of the University of Sydney, working with Professor Ethan Goddard Borger at WEHI and Associate Professor Nichollas Scott from the University of Melbourne and the Peter Doherty Institute for Infection and Immunity.
Professor Payne is also set to lead the newly announced Australian Research Council Centre of Excellence for Advanced Peptide and Protein Engineering. This center will build on discoveries like this one to speed the transition from basic research to applications in biotechnology, agriculture, and conservation.
"This study shows what's possible when we combine chemical synthesis with biochemistry, immunology, microbiology and infection biology," Professor Payne said. "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. That opens the door to new ways of treating some devastating drug-resistant bacterial infections."
Why a Bacterial Sugar Is a Unique Target
The antibody developed by the team targets a sugar molecule called pseudaminic acid. Although it resembles sugars found on human cells, this molecule is made only by bacteria. Many dangerous pathogens use it as a key part of their outer surface, helping them survive and evade immune defenses.
Because the human body does not produce this sugar, it offers a highly specific target for developing immunotherapies that avoid harming healthy cells.
Designing a Broad Acting Antibody
To take advantage of this weakness, the researchers first synthesized the bacterial sugar and sugar decorated peptides entirely from scratch. This work allowed them to determine the molecule's exact three dimensional structure and how it appears on bacterial surfaces.
Using this detailed information, the team created what they describe as a "pan-specific" antibody. It can recognize the same sugar across many different bacterial species and strains.
In mouse infection studies, the antibody successfully cleared multidrug resistant Acinetobacter baumannii. This bacterium is a well known cause of hospital acquired pneumonia and bloodstream infections and is especially difficult to treat.
"Multidrug resistant Acinetobacter baumannii is a critical threat faced in modern healthcare facilities across the globe," Professor Goddard-Borger said. "It is not uncommon for infections to resist 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."
How Passive Immunotherapy Could Protect Patients
Passive immunotherapy involves giving patients ready made antibodies to quickly control an infection, rather than waiting for the body's adaptive immune system to respond. This approach can be used both to treat active infections and to prevent them.
In hospital settings, it could be used to protect vulnerable patients in intensive care units who are at high risk from drug resistant bacteria.
Associate Professor Scott noted that the antibodies also offer an important new way to study 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 recognise them lets us map where they appear and how they change across different pathogens. That knowledge feeds directly into better diagnostics and therapies."
Moving Toward Clinical Use
Over the next five years, the team plans to turn these findings into antibody treatments ready for use in the clinic, with a focus on multidrug resistant A. baumannii. Achieving this goal would remove one of the most dangerous members of the ESKAPE pathogens and mark a significant step forward in the global effort to fight antimicrobial resistance.
"This is exactly the kind of breakthrough the new ARC Centre of Excellence is designed to enable," Professor Payne said. "Our goal is to turn fundamental molecular insight into real-world solutions that protect the most vulnerable people in our healthcare system."
The authors declare no competing interests. Funding was received from the National Health and Medical Research Council; Australian Research Council; National Institutes of Health; the Walter and Eliza Hall Institute of Medical Research; Victorian State Government. Researchers acknowledge support of the Melbourne Mass Spectrometry and Proteomics Facility at the Bio21 Molecular Science and Biotechnology Institute.
All animal handling and procedures were conducted in compliance with the University of Melbourne guidelines and approved by the University of Melbourne Animal Ethics Committee (application ID 29017).
Journal Reference:
- Arthur H. Tang, Niccolay Madiedo Soler, Kristian I. Karlic, Leo Corcilius, Caitlin E. Clarke-Shepperson, Christopher Lehmann, Aleksandra W. Debowski, Ashleigh L. Dale, Lauren Zavan, Michelle Cielesh, Adedunmola P. Adewale, Karen D. Moulton, Lucy Li, Chenzheng Guan, Christopher McCrory, Maria Kaparakis-Liaskos, Benjamin P. Howden, Norelle L. Sherry, Ruohan Wei, Xuechen Li, Ruth M. Hall, Johanna J. Kenyon, Linda M. Wakim, Francesca L. Short, Danielle H. Dube, Stuart J. Cordwell, Mark Larance, Keith A. Stubbs, Glen P. Carter, Nichollas E. Scott, Ethan D. Goddard-Borger, Richard J. Payne. Uncovering bacterial pseudaminylation with pan-specific antibody tools. Nature Chemical Biology, 2026; DOI: 10.1038/s41589-025-02114-9
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