Sugar, AR’s Goin Down

Antibiotic resistance (AR) continues to be an emerging threat across the globe. If we lose the ability to use certain antibiotics, it could leave millions across the globe with life-threatening conditions and illnesses. Dangerous bacteria in the gut – emboldened by AR – can affect pre-existing conditions, such as IBD, or threaten the lives of those living in the developing world through diarrhea.

Various studies have sought out to establish new antibiotics to replace those made ineffective by AR, but a new paper has established how the bacteria thrives in our intestines (1). “We hypothesized that dangerous bacteria need specific nutrients to establish themselves in their host’s intestine, before they can cause disease,” says Qiaochu Liang, PhD candidate at University of British Columbia (UBC) and first author on the study. “We hoped that, by identifying these nutrients, they would represent novel treatment targets for intestinal infections and chronic diseases linked to gut bacteria.”

The study focused on Citrobacter rodentium – a pathogen unique to mice – that displays similar behavior to human E. coli. “They are very similar to pathogenic E. coli in terms of the types of sugars they prefer to consume,” Liang explains, “This makes Citrobacter rodentium an excellent tool to understand how pathogenic bacteria behave in the host, as most clinically important pathogens are unable to infect mice.” 

The team were able to identify sialic acid – a sugar derived from mucus in the intestine – as a key factor in bacterial gut infection. “This provides a crucial foundation for our ongoing efforts to discover ways to inhibit the ability of these pathogens to sense and access this sugar, as well as identify good bacteria (probiotics) that can outcompete the pathogenic bacteria by outcompeting them for these sugars,” adds Hongbing Yu, UBC research associate and co-author.

By removing Citrobacter rodentium’s ability to use sialic acid, the team was able to worsen the bacteria’s overall ability to infect – including stymying its growth and lessening its ability to surpass our gut’s defense mechanisms.

“In addition to consuming sialic acid as a nutrient, Citrobacter rodentium also use the sugar as a signal to trigger the production of two special virulence proteins that help them cross the mucus layer and stick to the cells that line the gut,” says Bruce Vallance, Professor in the Department of Pediatrics at UBC and senior author on the study. “This discovery has given us insights into the role of sugars and highlights how the pathogenic bacteria are able to use host derived nutrients for their survival and to overcome our body’s defenses.”

This research may see sialic acid become a crucial actor in the fight against antibacterial resistance. If the sugar is crucial for the survival of dangerous bacteria, then targeting sialic acid may be a potential avenue for treatment.

“Targeting sialic acid could be a way to treat or prevent diseases by reducing the energy sources for these bacteria, as well as impairing their ability to cross the colonic mucus layer to interfere with the underlying epithelial cells,” says Vallance. “For pathologists and laboratory professionals, our findings highlight the critical role played by intestinal mucus in promoting a variety of intestinal diseases.”

“Thus, fixatives that preserve the mucus layer, and mucin-dwelling bacteria in intestinal biopsies may provide additional key information in defining the causes of intestinal diseases,” adds Vallance.