Custom Antibiotics

In the hunt for new ways to kill harmful bacteria, scientists have turned to a natural predator: viruses that infect them. By tweaking the genomes of these predatory viruses, known as bacteriophages, researchers hope to customize them in order to target any type of pathogenic bacteria.

To help achieve that goal, MIT biological engineers have devised a new mix-and-match system to genetically engineer viruses to attack specific bacteria. This approach could generate new weapons against bacteria for which there are no effective antibiotics, says Timothy Lu, an associate professor of electrical engineering and computer science and of biological engineering.

“These bacteriophages are designed in a way that’s relatively modular. You can take genes and swap them in and out and get a functional phage that has new properties,” says Lu, the senior author of a recent paper describing this work.

The Food and Drug Administration has approved a handful of bacteriophages for treating food products, but efforts to harness them for medical use have been hampered because isolating useful phages from soil or sewage can be a tedious, time-consuming process.

The MIT researchers set out to create a standardized genetic scaffold for their phages, which they could then customize by replacing the one to three genes that control the phages’ bacterial targets.

Many bacteriophages consist of a head region attached to a tail that enables them to latch onto their targets. The MIT team began with a phage from the T7 family that naturally kills E. coli. By swapping in different genes for the tail fiber, the researchers generated several phages, each targeting a different type of bacteria.

“You keep the majority of the phage the same and all you’re changing is the tail region, which dictates what its target is,” Lu says.

In this study, the researchers engineered phages that can target pathogenic Yersinia and Klebsiella bacteria, as well as several strains of E. coli. These are all part of a group known as Gram-negative bacteria, which includes strains against which there are few new antibiotics. So it should be feasible to create phages targeting other microbes in the group, including those that can cause pneumonia, sepsis, gastritis, Legionnaires’ disease, and other respiratory, urinary, and gastrointestinal infections.

One advantage of these engineered phages is that unlike many antibiotics, they are very specific in their targets. “Antibiotics can kill off a lot of the good flora in your gut,” Lu says. “We aim to create effective and narrow-spectrum methods for targeting pathogens.”