The National Institutes of Health’s National Institute of Biomedical Imaging and Bioengineering has awarded Cornell a $2.6 million grant to study bacteriophages – microscopic foot soldiers in the fight against pathogenic bacteria.
“Bacteriophages are the naturally evolved predators that fight against bacteria, and they may be an important factor in defeating antibiotic-resistant bacteria,” said Sam Nugen ’99, Ph.D. ’08, associate professor of food and biosystems engineering and the grant’s principal investigator. “Once the antibiotic options run out, bacteriophages are the only thing left to fight bacteria.”
A bacteriophage, or phage, is a virus that infects a bacterium. Phages are the “perfect predators,” Nugen said, since they are harmless to humans and can be engineered as tools to separate, concentrate, detect and destroy bacterial hosts.
The technology will allow the rapid and low-cost detection of E. coli in drinking water for use in low-resource settings, such as sub-Saharan Africa. Additionally, phages have already been used to treat patients infected with multidrug resistant bacteria, which in some cases, allows patients to make full recoveries, Nugen said.
The researchers will examine ways for phages to detect bacterial enemies, which includes developing magnetic phages for bacteria detection and separation, and using machine learning to model phage-bacteria binding and create a customized range of bacterial hosts.
Working stealthily, the bacteriophage T7NLC, for example, carries a gene for an enzyme called luciferase, which is similar to the protein that gives fireflies luminescence. The luciferase is fused to a carbohydrate binder, so that when the bacteriophage finds the bacteria E. coli in water, an infection starts and the fusion enzyme is created. When released, the enzyme sticks to cellulose fibers and begins to luminesce.
After the phage binds to the E. coli, it shoots its DNA into the bacteria and begins an infection cycle, ultimately killing the host bacteria. “That is the beginning of the end for the E. coli,” said Nugen.
The bacteriophage then breaks open the bacterium, releasing the enzyme as well as additional phages to attack and destroy other E. coli.
“We are hoping for phage-based tools with increased functionality and customizable host ranges,” Nugen said. “The threat of bacterial infections, including infection with multi-drug resistance, continues to grow. So phages, which have evolved to efficiently recognize and kill bacteria, will become an indispensable tool for medicine.”
In addition to the medical world, Nugen said, phages can be used for food safety to track and kill bacteria in meat and vegetable food preparation.
“The ability to rapidly design and engineer new phages for biosensing and therapeutics will be a critical advantage to human health,” he said. “The technologies being developed will allow researchers to tip the scales of the co-evolutionary arms race between phages and bacteria.”
Joining Nugen on the grant will be Cornell’s Julie Goddard ’99, Ph.D. ’08, associate professor of biomaterials and biointerfaces in food systems; Martin Wiedmann, Ph.D. ’97, the Gellert Family Professor in Food Safety; Joseph Peters, professor of microbiology; and Haiyuan Yu, professor at the Weill Institute for Cell and Molecular Biology; Joey Talbert, M.S. ’04, Ph.D. ’08, from Iowa State University; Betty Kutter, from Evergreen State College; and Lone Brøndsted, from the University of Copenhagen.