Preemptive strike

A new way to destroy bacteria before they cause infection has been found

Maria Krivochenko, Naked Science

Antibiotic-resistant bacteria, such as ExPEC ST131 (e x traintestinal p athogenic E scherichia c oli s equence t ype 131), can colonize the human intestine without provoking disease. However, they can infect other organs. Thus, they are associated with infections of the urinary tract, brain, peritoneum, peripheral organs, blood and internal devices such as urinary catheters, feeding tubes and wound drains.

Researchers at Baylor College of Medicine have identified a new strategy that eliminates bacteria before they cause infection. The method uses bacteriophages that are able to be located close to microorganisms in the gastrointestinal tract - this facilitates the attack and subsequent destruction of bacteria. Details of the work are published in the journal mBio (Green et al., Targeting of Mammalian Glycans Enhances Phage Predation in the Gastrointestinal Tract).

The team found out that mucins, sticky glycoproteins that form a layer between intestinal epithelial cells and a layer of microorganisms, do not allow bacteriophages to destroy bacteria in the intestines of mammals.

The scientists then tested human wastewater and animal feces for the presence of bacteriophages with unique properties that support the ability to destroy bacteria in the presence of mucins. So they discovered a new phage called ES17: it binds to mucins and therefore can destroy bacteria in compound-rich environments. Further studies have shown that ES17 binds to heparan sulfate polysaccharide molecules, which can be found not only in mucins, but also on the surface of various cell types, including epithelial cells.

This prompted the researchers to find out whether binding heparan sulfate to epithelial cells would help ES17 target and destroy bacteria in the intestinal environment. Biologists tested the effect of the ES17 phage on its bacterial host ExPEC in the mouse intestine and compared it with the effect of phages that are unable to infect the host under difficult conditions.

"We found that only ES17 has the unique ability to target and eliminate bacteria in animal models," said Dr. Sabrina Green, author of the work. Researchers suggest that bacteriophages are able to do this before microorganisms infect organs.

"We foresee that positional targeting will become the way smart medicines work in the future. The drugs will not just be distributed throughout the body in the hope that a part will be in the right place. They will be delivered only to where they are supposed to work. Our work with phages is the first time that such a thing has been done," concluded Anthony Maresso, co–author of the study.

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