A unique sugar found only on the surface of bacteria is emerging as a promising target in the fight against antibiotic-resistant superbugs, offering a potential new avenue for immunotherapy development. Researchers in Australia have engineered antibodies to recognize this bacterial sugar, effectively flagging the pathogens for destruction by the immune system – a strategy that has shown success in eliminating infections in laboratory mice.
The rise of multidrug-resistant bacteria poses a critical threat to global health, rendering many common infections increasingly difficult, and sometimes impossible, to treat. The World Health Organization lists several of these pathogens, including Acinetobacter baumannii, as “critical priority” threats [1]. This new approach, detailed in a study published in Nature Chemical Biology, bypasses the mechanisms bacteria use to resist traditional antibiotics, offering a potential solution to this growing crisis.
Targeting the Unique Bacterial Surface
The key to this breakthrough lies in pseudaminic acid, a sugar molecule found exclusively on the outer surface of certain bacteria [3]. Unlike human cells, bacteria displaying this sugar are vulnerable to antibodies specifically designed to bind to it. Researchers, led by Professor Richard Payne of the University of Sydney, created these antibodies in the lab, effectively creating a “guided missile” for the immune system [1].
“By designing antibodies that recognize this unique sugar, researchers were able to guide the immune system to attack and eliminate deadly infections that normally shrug off antibiotics,” explained the University of Sydney in a press release [5]. The antibodies bind to the bacterial sugar, signaling to the immune system that the bacteria are foreign and should be destroyed.
Success in Preclinical Trials
The effectiveness of this strategy was demonstrated in preclinical trials using mice infected with drug-resistant Acinetobacter baumannii [3]. The engineered antibodies successfully eliminated the infection, preventing what would normally be a fatal outcome. This success suggests the potential for developing similar immunotherapies for human infections acquired in hospitals, where antibiotic resistance is particularly prevalent.
This isn’t the first time saccharin has been linked to antibacterial properties. A 2025 study published in EMBO Molecular Medicine found that saccharin, a common artificial sweetener, also exhibits antimicrobial activity against some drug-resistant bacteria [4]. While the mechanisms differ – saccharin directly impacts bacterial growth and morphology – both discoveries highlight the potential of unexpected compounds in combating antibiotic resistance.
Beyond Antibodies: A Broader Approach
The research team, a collaboration between the University of Sydney, WEHI, and the University of Melbourne’s Peter Doherty Institute for Infection and Immunity, is now focused on translating these findings into clinical applications [1]. Professor Payne is also leading the newly established Australian Research Council Centre of Excellence for Advanced Peptide and Protein Engineering, suggesting a continued commitment to this area of research [1].
The approach differs significantly from traditional antibiotics, which often target essential bacterial processes, leading to the development of resistance. By focusing on a sugar unique to bacteria, the immunotherapy aims to minimize harm to human cells and offer a more targeted treatment. Unlike antibiotics, this method delivers pre-made antibodies to quickly neutralize infections, offering both treatment and potential preventative measures for high-risk patients [3].
What’s Next in the Fight Against Superbugs?
While these findings are promising, further research is needed to determine the safety and efficacy of this immunotherapy in humans. Clinical trials will be crucial to assess the potential of this approach as a viable treatment option for antibiotic-resistant infections. The development of pan-specific antibodies, capable of binding to a range of bacterial sugars, could broaden the applicability of this strategy [3]. The ongoing work at the Australian Research Council Centre of Excellence for Advanced Peptide and Protein Engineering will likely play a key role in these future developments.
What are your thoughts on this new approach to fighting antibiotic resistance? Share your comments below, and let’s continue the conversation.
