Researchers at Baylor College of Medicine and other institutions have developed a new strategy that can kill bacteria in a particular area before they become infected. The strategy uses phage, a virus that infects and kills bacteria that can specifically place bacteria in the same place in the gastrointestinal tract. Proximity of phage և bacteria facilitates phage attack և subsequent elimination of bacteria.
This strategy could be a game changer in the fight against antibiotic-resistant bacteria that live in hard-to-reach places, such as the intestinal mucosa. The study appears in the journal mBio:,
“Fagers are very specific for their ability to infect or kill certain types of bacteria or strains, not just other good bacteria, such as good bacteria.” “In the United States, phage therapy is becoming more and more affordable for the treatment of antibiotic-resistant bacterial infections, which is a serious health problem,” said Dr. Sabrina Green, lead author of research and development at Baylor TAILFR Laboratories.
Antibiotic-resistant bacteria, such as ExPEC ST131, can colonize the human gut without causing disease, but they can also come out of the gut and infect other organs. For example, these bacteria are associated with leakage from the urinary tract, brain, peritoneum, peripheral organs, blood և living devices such as urinary catheters, vascular devices, feeding tubes,, which causes 9 million infections a year. ,
In previous work, the team has shown that phages can effectively treat infections caused by ExPEC ST131 bacteria. In this study, they wanted to see if they could use phages to remove those bacteria to prevent infection.
Finding a phage
Many phages find it difficult to fight off bacteria in the gut. The team found that there is a factor in mammalian intestines that prevents the killing of phage bacteria. They identified the factor as a mouse, a sticky protein that forms a layer of “microorganisms” between intestinal epithelial cells.
The researchers argued that although mucus prevents bacteria from infecting many phages, there may be those who have developed a way to counteract the effects of mucus, as a result of which they are able to target the bacteria in a highly mucous environment.
“We looked at human waste water, animal feces for phages with unique properties that facilitate their ability to kill bacteria in the presence of mucus,” said Dr. Anthony Mareson, Associate Professor of Baylor Molecular Virology and Microbiology. “We discovered a new phage called ES17, which is associated with mucus. This property seems to enhance its ability to infect bacteria in a mucus-rich environment, such as salt.”
Further studies looked more closely at this new phage-muscine interaction. Green, Mareson և and their colleagues discovered that phage ES17 binds to special molecules called heparan sulfate, which can be found not only in mucus but also on the surface of various cell types, including epithelial cells. This prompted researchers to investigate whether the binding of heparan sulfate to epithelial cells, which the researchers found to be the same binding site used by ESPEC-accepting ES17 bacteria, would enhance ES17’s ability to target and kill bacteria in the gut.
“We tested the effect of ES17 phage in the gastrointestinal tract on its bacterial host ExPEC, comparing it to phages that are known to be unable to infect their bacterial host in a complex environment,” Green said. “We found that only ES17 has the unique ability to target and kill ExPEC bacteria in animal models.”
A new strategy to prevent bacterial infections
In general, the findings suggest that the ability of phage ES17 to bind to liver sulfate on mucus-rich surfaces, directly on mammalian epithelial cells, mediates its localization in areas deep in the gut where there may be reservoirs of bacteria. Researchers suggest that being close to ExPEC bacteria facilitates the invasion of phages, the killing of bacteria before they can leave the gut, and infect other organs.
“Phages are viruses that specialize in invading and killing specific bacteria. Here we showed the first phage, also associated with human epithelial cells, that this property mediates a new mechanism in the fight against bacterial infections, which we call positional targeting, because it allows the phage to predict where it will be located. “The targeted bacteria,” said Mareson. “We anticipate that in the future, smart drugs will be targeted. Drugs simply do not spread throughout the body, hoping that some of them will end up in the right place. The medicines of the future will only go to the places where they are supposed to work. “Our work with Fager is the first time they have achieved this.”
Reference February 9, 2021, mBio.
DOI: 10.1128 / MB bio.03474-20
The other participants in this work are: Carmen Gu Lew, Xu Yang, Shelley Gibson, Wilhelm Salman, Anubama Rajan, Hannah E. Cards, Just Astin R. Clark, Kuzeng Song, Robert F. Ramig, Barbara W. Trout և Heidi B. Kaplan. The authors are related to one or more of the following institutions: Baylor Medical College, Emory University, Michael E. Debakey Veterans Medical Center համալս University of Texas Houston Health Science Center.
This work is partially supported by a grant from the Veterans Affairs of the United States (VA I01-RX002595), the Roderick D. MacDonald Research Fund at Baylor St. Lucas Medical Center, the Mike Hogg Foundation, and the Baylor College of Medicine Seed Fund.