Engineered Antibiotic Viruses Target Toxins To Bacteria

A new approach to killing harmful bacteria has been developed that uses engineered particles, known as “phagemids,” capable of producing toxins that are deadly to targeted bacteria.

Researchers at MIT, the Broad Institute of MIT and Harvard, and Harvard University revealed that they have developed a unuque way to combat the global rise in antibiotic resistance. The rise is a growing threat to public health, damaging our ability to fight deadly infections such as tuberculosis.

Bacteriophages (viruses that infect and kill bacteria) have been utilized for treating infection in countries such as those in the former Soviet Union for many years. In contrast conventional broad-spectrum antibiotics, these viruses target specific bacteria without harming the body’s normal microflora.

Bacteriophages, however, can also provoke potentially harmful side effects, says James Collins, of MIT’s Department of Biological Engineering and Institute of Medical Engineering and Science, who led the research.

“Bacteriophages kill bacteria by lysing the cell, or causing it to burst,” Collins says. “But this is problematic, as it can lead to the release of nasty toxins from the cell.”

Toxins which can lead to sepsis and even death in some cases, he says.

Collins previous research focused on engineering bacteriophages to express proteins which did not actually burst the cells, but rather increased the effectiveness of antibiotics when delivered at the same time.

The lastest sudy by his team builds on this earlier work, by setting out to come up with related technology to target and kill specific bacteria, without bursting the cells and releasing their contents.

Once inside the cell, the plasmids are engineered to express different proteins or peptides—molecules made up of short chains of amino acids—that are toxic to the bacteria, Collins says.

“We systematically tested different antimicrobial peptides and bacterial toxins, and demonstrated that when you combine a number of these within the phagemids, you can kill the great majority of cells within a culture,” he says.

The expressed toxins are designed to disrupt different cellular processes, such as bacterial replication, causing the cell to die without bursting open.

Russell J. Krom, Prerna Bhargava, Michael A. Lobritz, and James J. Collins
Engineered Phagemids for Nonlytic, Targeted Antibacterial Therapies
Nano Lett., Article ASAP DOI: 10.1021/acs.nanolett.5b01943

Illustration: phagemid plasmids infect a targeted bacteria. Credit: Christine Daniloff and Jose-Luis Olivares/MIT (plasmid illustration courtesy of the researchers)