Promising Approach To Stop Bacteria Binding to Host Cells Identified

As concerns about waning antibiotic effectiveness grow, researchers are using unique tools to search for new ways to keep bacteria from causing infections in both humans and animals.

“We’re really interested in finding out how bacteria make their connection with the host cells they’re going to infect,” says Dr. Peter Davies, professor of biochemistry and former Canada Research Chair in protein engineering at Queen’s University. Davies and his colleagues used the Canadian Light Source (CLS) at the University of Saskatchewan to visualize the structure of long, thin proteins called adhesins, which most bacteria have, and which bind to a sugar molecule on the surface of a cell. Once attached, “the bacteria start to form a colony and then eventually a biofilm. This is how they get started in an infection,” he explains.

The goal of the research, recently published in the journal Molecular and Cellular Biology, is to find a way to interrupt that attachment process -- to “put something in there that would fool them (bacteria) and not allow them to bind to the host cells.”

With the help of an artificial-intelligence (AI) program that can create a three-dimensional model of a protein, says Davies, “we’ve learned how to recognize those parts of the protein that stick to the surface of cells” and begin causing infections. The researchers noted one spot on the protein that attaches to a simple sugar called fucose found on human blood cells and other organisms.

Special imaging at the CLS – called crystallography -- confirmed the model and revealed a possible way to inhibit bacteria from binding to cells. In this research, Davies and colleagues were studying a bacterium called Aeromonas hydrophila, which can affect people who are immunocompromised.

Adding more fucose in with the bacterium disrupts the binding process “because they’re confused by all of this free fucose floating around,” says Davies. The protein sensors “that are looking out for the sugar on our cells” are unable to bind “because we’re flooding the market with fucose.”

The next steps in the research will be to produce compounds that mimic fucose “but that cannot be metabolized by either the bacteria or by the human cells that we’re trying to protect,” he says. “We won’t have to put so much sugar in the system.” Looking down the road, he believes there is potential to patent, protect and market these fucose analogs. “We’re thinking about how we can make this into a drug that will replace antibiotics to some extent.”

Davies is very optimistic about the future potential of this approach to fighting bacterial infections “because it gets to the colonization right at the very beginning. If you block these bacteria from making the first contact with human cells, then they will never get established.”

Reference: Ye Q, Eves R, Vance TDR, et al. Aeromonas hydrophila RTX adhesin has three ligand-binding domains that give the bacterium the potential to adhere to and aggregate a wide variety of cell types. mBio. 2025;16(5):e03158-24. doi: 10.1128/mbio.03158-24

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