Scientists uncover an Achilles’ heel in deadly superbugs — and a way to exploit it

Antibiotic-resistant bacteria may have an Achilles’ heel: a unique sugar molecule found only on the outsides of bacterial cells.

Targeting this molecule can make the bacteria vulnerable to the immune system, which can then destroy the germs and clear infections, recent research in mice shows.

If the same effect can be demonstrated in humans, targeting this sugar molecule could offer a new approach to tackling a wide array of superbugs — including notorious species like Acinetobacter baumannii, Helicobacter pylori, and Campylobacter jejuni. That’s according to the researchers behind the study, which was published Feb. 4 in the journal Nature Chemical Biology.

“The next stage in the development of this concept is to produce an antibody that is suitable for use in humans,” said study co-author Ethan Goddard-Borger, who studies the role of sugars called glycans in disease at the Walter and Eliza Hall Institute of Medical Research in Australia.

This would involve either “humanizing” the antibody used in their mouse study or identifying a human equivalent that is similarly potent, Goddard-Borger told Live Science in an email.

Sugars on superbugs

Antibiotic-resistant ​​bacteria​​ pose a critical threat worldwide, and Gram-negative bacteria are a particular problem. Bacteria within this group sport tough protective layers that make them especially hard to treat with many existing drugs. The pathogens A. baumannii, H. pylori and C. jejuni belong to this group.

These bacteria often employ a “sugar coat” to help them evade the immune system and resist the effects of antibiotics. The sugar coating essentially mimics sugars seen on human cells, tricking the immune system into ignoring the bacteria.

Past research showed that a sugar called pseudaminic acid (Pse) is found exclusively on the outsides of bacterial cells, and that it differs significantly from sugars found on human cells. Theoretically, this could make Pse a safe way to target infections that are resistant to antibiotics, by helping flag the bacteria as “foreign” so the immune system can attack them.

However, previous research was limited in that scientists struggled to extract enough of the sugar to study it effectively. So in the new study, the researchers ​​made Pse sugar molecules in the lab.

They used the tailor-made molecules to develop specialized proteins that latch onto them. These proteins, called monoclonal antibodies, ​​act like a highly specific biological targeting system, designed to home in on the Pse sugars.

In lab experiments, ​​the team tested these antibodies against H. pylori, C. jejuni, and A. baumannii and found that ​​they​​ tightly bound Pse across all of those bacterial species. The antibodies worked even when the sugars differed in structure between the bacteria.

Next, they tested the sugars in mice with antibiotic-resistant A. baumannii infections. They found that tagging Pse with antibodies​​ made the infections visible to the immune system, enabling immune cells to find, engulf, and destroy the bacteria.

In an experiment, 10 mice that didn’t receive the antibodies died of their infections within a day. Mice treated with the antibodies had 100% survival through a full week of observation.

A new approach to beat antibiotic resistance?

The study authors think that, in the future, these antibodies could be given to vulnerable hospital patients to help prevent infections. Since Pse is absent in human cells, they expect such a therapy would specifically target bacteria without harming healthy human cells.

In the long term, the authors propose, these antibodies could potentially be utilized to develop vaccines that offer broad protection against Gram-negative bacteria.

The immediate next step, though, involves adapting these antibodies for potential human use. “I do think that it may be possible to develop monoclonal antibodies that target shared sugars across multiple bacteria to be used as a therapeutic,” said Brian Luna, assistant professor of molecular microbiology and immunology at the University of Southern California, who was not involved in the study.

“However, the main limitation is that the sugars, including pseudaminic acid in this case, are not expressed on all bacteria,” Luna told Live Science in an email. “So while this antibody may hit some specific strains across different bacterial species, additional work would be needed to show that these antibodies bind a high percentage of clinical isolates tested for this specific antibody to be reasonably considered as a potential therapeutic.”

In short, much more work is needed to demonstrate that such antibodies could help treat and prevent a wide range of bacterial infections in people.