Study recreates biological microenvironments and demonstrates effectiveness of phage therapy as an alternative to antibiotics

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According to a study published in PLoS Biology. The study also found that some E. coli cells from these microenvironments were able to survive phage treatment without acquiring genetic resistance.

Phage therapy is the use of viruses, called bacteriophages, to kill bacteria instead of antibiotics. An increasing number of bacterial infections, including pneumonia, tuberculosis, gonorrhea and salmonellosis, are becoming highly resistant to antibiotics, resulting in higher death rates, longer hospital stays and higher medical costs. Bacteriophages do not pose a threat of human infection and could therefore serve as an alternative to antibiotics in infections that have become genetically resistant.

“Antibiotic resistance could prove to be more deadly than COVID-19 if we don’t find new ways to fight the infection,” Stefano Pagliara, PhD, said in a press release. “Phage therapy shows great promise as part of the picture, and our research has overcome some of the hurdles so far, by mimicking the behavior of bacteria in the small vessels of our bodies. If phage therapy could one day become even a small part of routine care, it could help save thousands of lives.

Until this study, the majority of experiments focused on exposing bacteria to phages in a vial, investigators said. In this environment, bacteria interact and evolve rapidly, modifying their DNA and becoming resistant to phages. The vials do not mimic the functioning of bacteria in organs such as the lungs, where they exist in microenvironments such as capillaries or alveoli. The current study has replicated these microenvironments and introduced phages into each compartment in turn instead of mixing with large numbers of bacteria.

Thanks to this method, the investigators found that E. coli the cells of these simulated microenvironments do not become genetically resistant to phages and the majority of the bacterial population is killed. They also found that the bacteria that survived did not acquire genetic resistance, but instead showed fewer phage receptors, meaning that phages have less access to these cells than the rest of the bacterial population.

“A key aspect of whether phage can kill bacteria is the number of phage receptors bacteria have,” Edze Westra, PhD, MSc, said in the release. “More receptors mean a better chance of defeating bacteria by phage. Our research indicates that if we can find new ways to promote phage receptor production in bacteria, we may improve the prospects for phage therapy as a viable alternative to antibiotics.

THE REFERENCES

Phage therapy research brings scientists closer to mastering viruses to fight antibiotic resistance [news release]. EurekAlert; October 12, 2021. Accessed October 19, 2021. https://www.eurekalert.org/news-releases/931236


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