New lab-made antibody targets drug-resistant bacteria

Australian researchers have announced a promising strategy to combat deadly, drug-resistant bacteria by designing antibodies that target a sugar found only on bacterial cells. The discovery could form the foundation for a new generation of immunotherapies aimed at multidrug resistant hospital-acquired infections.

The study demonstrates that a laboratory-made antibody can eliminate an otherwise lethal bacterial infection in mice. The antibody works by recognising a distinctive bacterial sugar and flagging the pathogen for destruction by the immune system.

Targeting a bacterial sugar

The new antibody targets a sugar molecule known as pseudaminic acid. Although it resembles sugars found on human cells, pseudaminic acid is produced exclusively by bacteria. Many dangerous pathogens use it as an essential component of their outer coats to evade immune responses.

Because humans do not produce this sugar, it offers a highly selective target for immunotherapy development. To exploit this vulnerability, the team chemically synthesised the bacterial sugar and sugar-decorated peptides from scratch. This approach allowed them to determine the molecule’s exact three-dimensional arrangement and how it appears on bacterial surfaces.

Using this knowledge, the researchers developed a ‘pan-specific’ antibody capable of recognising the sugar across a wide range of bacterial species and strains.

Successful tests against multidrug-resistant infections

In mouse models, the antibody successfully eliminated multidrug-resistant Acinetobacter baumannii, one of the main causes of hospital-acquired pneumonia and bloodstream infections.

“Multidrug resistant Acinetobacter baumannii is a critical threat faced in modern healthcare facilities across the globe,” said research collaborator Professor Ethan Goddard-Borger at the Walter and Eliza Hall Institute of Medical Research (WEHI) 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.”

Passive immunotherapy involves giving ready-made antibodies to control an infection quickly, rather than waiting for the patient’s adaptive immune system to respond. It can be used both therapeutically and prophylactically, potentially protecting vulnerable patients in intensive care units.

A tool for understanding bacterial virulence

“These sugars are central to bacterial virulence, but they’ve been very hard to study,” said research collaborator Nichollas Scott, Associate Professor at the University of Melbourne. “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.”

The team plans to translate these findings into clinic-ready therapies for multidrug-resistant A. baumannii over the next five years. Success would effectively remove the ‘A’ from the ESKAPE pathogens, which would be crucial in the global fight against antimicrobial resistance.

“This study shows what’s possible when we combine chemical synthesis with biochemistry, immunology, microbiology and infection biology,” said research co-leader and Professor at the University of Sydney, Richard Payne. “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.”