As drug‑resistant hospital infections continue to rise worldwide, a team of Australian researchers has identified a surprising new bacterial vulnerability: a sugar that only microbes make. By designing antibodies that recognize this sugar, the scientists were able to clear lethal infections in mice—offering a potential new strategy for tackling multidrug‑resistant pathogens.
The work, published in Nature Chemical Biology, describes the development of monoclonal antibodies that target pseudaminic acid, a carbohydrate found on the surface of many dangerous bacteria but absent from human cells. The study, titled “Uncovering bacterial pseudaminylation with pan‑specific antibody tools,” demonstrates that this sugar may serve as a highly selective molecular flag for immunotherapy.
Pseudaminic acid is structurally similar to human sugars, yet bacteria use it as a key component of their outer coats, where it contributes to virulence and immune evasion. That exclusivity makes it an appealing therapeutic target. But until now, researchers lacked tools to detect or study it broadly across species.
To overcome that barrier, the team first synthesized pseudaminic acid and pseudaminylated peptides from scratch. “This study shows what’s possible when we combine chemical synthesis with biochemistry, immunology, microbiology, and infection biology,” said co‑lead author Richard Payne, PhD, of the University of Sydney. Building the sugars in the lab allowed the researchers to determine their three‑dimensional structure, how they present on bacteria, and design “pan-specific” antibodies that bind them with high specificity. “That opens the door to new ways of treating some devastating drug‑resistant bacterial infections,” Payne added.
The resulting “pan‑specific” antibodies recognize pseudaminic acid in multiple chemical contexts and across diverse bacterial species. Using these tools, the researchers mapped pseudaminylated proteins in Helicobacter pylori, Campylobacter jejuni, and Acinetobacter baumannii—pathogens in which the sugar plays a central role in virulence. Associate professor Nichollas Scott, PhD, a co‑author from the University of Melbourne, noted that these sugars have long been difficult to study. “Having antibodies that can selectively recognize them lets us map where they appear and how they change across different pathogens,” he said. “That knowledge feeds directly into better diagnostics and therapies.”
The most striking results came from mouse infection models. When administered to animals infected with multidrug‑resistant A. baumannii, the antibodies enhanced phagocytosis and cleared the otherwise lethal infection. Another co-author, Ethan Goddard‑Borger, PhD, of Walter and Eliza Hall Institute of Medical Research (WEHI), emphasized the clinical significance: “Multidrug‑resistant Acinetobacter baumannii is a critical threat faced in modern healthcare facilities across the globe. 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.”
Because pseudaminic acid is not produced by humans, therapies targeting it could offer a highly selective way to neutralize pathogens without harming host tissues. The approach could someday be used both therapeutically and prophylactically, potentially protecting vulnerable patients from deadly infections.
The team plans to advance these antibodies toward clinical development over the next five years, with a particular focus on A. baumannii. If successful, the strategy could remove one of the most problematic “A” pathogens from the ESKAPE group—an important milestone in the global fight against antimicrobial resistance.
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