Engineered Viruses Enhance Drug Activity

Bacteriophages help drugs knock out bugs

Untreated E. coli bacteria; initial magnification 5,000 times.

Engineered viruses can knock out the defense systems in bacteria, enhancing the efficacy of antibacterial agents, researchers have found.

These bacteriophages—viruses that attack bacteria—can enhance the killing of resistant organisms and serve as helpful adjuvants to existing antibiotics, researchers at Boston University and the Harvard-Massachusetts Institute of Technology Division of Health Sciences and Technology report.

"The Food and Drug Administration (FDA) has approved bacteriophage therapy for use on food—there have been sprays for Listeria, for example—but there’s never been a bacteriophage approved for clinical use," said Timothy Lu, PhD, first author of the paper and a medical student at Harvard, in an interview with PFQ.

By engineering bacteriophages to attack genes in bacteria that are not directly targeted by antibiotics, the researchers enhanced the efficacy of quinolone, aminoglycoside, and beta-lactam antibiotics against E. coli by several orders of magnitude in vitro and increased the survival of infected mice in vivo. (Lu TK, Collins JJ. Engineered bacteriophage targeting gene networks as adjuvants for antibiotic therapy [published online ahead of print March 2, 2009]. Proc Natl Acad Sci U S A.)

The Food and Drug Administration has approved bacteriophage therapy for use on food—there have been sprays for Listeria, for example—but there’s never been a bacteriophage approved for clinical use.

—Timothy Lu, PhD, Harvard University

The researchers hope the fact that they are working with existing antibiotics rather than novel drug entities will help speed this technology to the clinic, Dr. Lu said.

He added that the researchers showed that formulating the combination of the engineered bacteriophage with the antibiotics was not a difficult process. “In our experiments, they were just mixed into the same liquid solutions, which worked well in vivo and in vitro,” Dr. Lu said.

A potential advantage of the use of bacteriophage in an adjuvant role is that, as bacteria continue to evolve resistance, the bacteriophage can be evolved to attack the newly resistant entities, Dr. Lu said.

Dr. Lu also said, however, that evolving bacteriophages might pose a challenge to the FDA. "Will evolved bacteriophage constitute completely new entities? Resistance is an ever-evolving process, and perhaps the current method for developing and approving drugs is not the most adaptive."