Researchers at the University of Sydney, Australia, have developed a promising strategy to combat bacteria that no longer respond to antibiotics.
The work, published in the journal Nature Chemical Biology, shows that antibodies created in the laboratory can eliminate normally fatal bacterial infections in mice.
The strategy works by focusing on a sugar found only on the surface of bacterial cells.
Antibodies bind to this molecule and alert the immune system to destroy the invading pathogen.
According to Daily Science, this approach could lead to a new generation of hospital-acquired immunotherapies.
The target sugar is called pseudaminic acid. Although it resembles sugars found in human cells, this molecule is only produced by bacteria.
Many dangerous pathogens use it as an essential 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 damaging healthy cells.
How antibodies were developed
The team, led by Professor Richard Payne from the University of Sydney, worked with fellow professors Ethan Goddard-Borger, from Wehi (Australia’s oldest medical research institute), and Nichollas Scott, from the University of Melbourne and the Peter Doherty Institute for Infection and Immunity.
The researchers synthesized bacterial sugar and sugar-decorated peptides completely from scratch. This work allowed us to determine the exact three-dimensional structure of the molecule and how it appears on bacterial surfaces.
With this detailed information, the team created what they describe as a “pan-specific” antibody. It can recognize the same sugar in many different bacterial species and strains.
Test results
In mouse infection studies, the antibody successfully eliminated .
This bacteria is a well-known cause of hospital-acquired pneumonia and bloodstream infections, and is especially difficult to treat.
“Multi-drug-resistant Acinetobacter baumannii is a critical threat facing modern healthcare facilities around the world. It is not uncommon for infections to be resistant to even antibiotics,” said Professor 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.”
Passive immunotherapy
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 to both treat active infections and prevent them.
In hospital settings, it could be used to protect vulnerable patients in intensive care units who are at high risk of infections from drug-resistant bacteria.
Scott noted that antibodies also offer an important way to study how bacteria cause disease.
“These sugars are central to bacterial virulence, but they have been very difficult to study. Having antibodies that can selectively recognize them allows us to map where they appear and how they change in different pathogens. This knowledge directly feeds into better diagnostics and therapies.”
Next steps
Over the next five years, the team plans to turn these discoveries into clinical-ready antibody treatments, with a focus on multidrug-resistant Acinetobacter baumannii.
Achieving this goal would remove one of the most dangerous members of the Eskape pathogens and mark a significant step in the global effort to combat antimicrobial resistance.
Payne also leads the recently announced Australian Research Council Center of Excellence for Advanced Peptide and Protein Engineering. This center will build on discoveries like these to accelerate the transition from basic research to applications in biotechnology, agriculture and conservation.
“This is exactly the kind of advancement that the new Center of Excellence was designed to enable. Our goal is to transform fundamental molecular knowledge into real-world solutions that protect the most vulnerable people in our healthcare system.”
