In the front lines of combat between scientists and bacteria, there’s a notorious group of bugs that belong to a nefarious organization known as ESKAPE. These bacteria are particularly good at evading the effects of antibiotics, making them a major cause of hard-to-treat infections, often transmitted during hospital stays. The acronym that classifies them consists of the first letters of the six bacteria that belong to the group: Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species.
For years, scientists have sought ways to bust up this group of drug-resistant bugs as well as others that are able to sidestep our ever-evolving ways to kill them. We’ve seen, for example, shape-shifting antibiotics, golden pills, titanium spikes, molecular tweezers, and dozens of other strategies that seek to give us the upper hand in winning the war against these tiny but deadly adversaries.
Now, researchers from multiple universities and research institutes in Australia have added another potential weapon to the war against drug resistant bacteria: sugar. In particular, a class of sugars known as pseudaminic acids.
These sugars, while similar to some found in humans, are only produced by certain bacteria, where they help the bugs move, stick to host tissue, and avoid detection by the immune system. They’ve been found coating the surfaces of various disease-causing bugs including Helicobacter pylori, Campylobacter jejuni, and the drug-resistant A. baumannii.
However, studying and targeting these sugars has been challenging for scientists, who’ve only been able to work with bacteria containing an abundance of them.
The Australian researchers, however, overcame this problem by building the sugars from scratch instead of studying them on the surface of bacteria. Then they coated short chains of amino acids called peptides with them and by divorcing the sugars from the bacteria were able to train antibodies to recognize them even when they’re in complicated configurations on the surfaces of the bugs.
“These sugars are central to bacterial virulence, but they’ve been very hard to study,” said study co-author Nicollas Scott from 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.”
Indeed, testing these newly trained antibodies in mice infected with A. baumannii showed that they were successful in eliminating the pathogen and keeping the rodents safe from its effects, which can include pneumonia and infections in the bloodstream. In effect, the sugar acted as a beacon that guided the antibodies to their target.
“Multidrug resistant Acinetobacter baumannii is a critical threat faced in modern healthcare facilities across the globe,” said study co-author Ethan Goddard-Borger from the Walter and Eliza Hall Institute of Medical Research, Australia’s oldest medical research institute. “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.”
The team now plans to take the next five years to translate their study into immunotherapy medication that can be given in the real world to combat A. baumannii. If they’re successful, at least one letter will be eliminated from the deadly ESKAPE group.
The research has been published in the journal, Nature Chemical Biology.
Source: The University of Sydney