Engineered Virus Rids Bacteria of Antibiotic Resistance

Bacteria are growing ever more resistant to antibiotics, and there are mounting fears that soon our drugs won’t be able to fight even the most common infections. In the U.S. alone, more than 2 million people a year are infected by antibiotic resistant strains and over 20,000 die as a result.

In a bid to give our drugs a second chance, researchers from the Sackler School of Medicine in Tel Aviv have engineered viruses to infect resistant bacteria with a CRISPR-Cas9 system that eliminates the genes that code for antibiotic resistance. To ensure those modified bacteria pass on their antibiotic-susceptible genes, the scientists also had the virus deliver a set of beneficial genes that encode another CRISPR sequence to defend against infection by other viruses.

E coli Ag Res Mag
Researchers tested their CRISPR systems in E. coli, seen here under magnification.

It’s a fitting application for the powerful gene editing technique since it was originally discovered in microbes. In its native habitat, CRISPR recognizes sequences of viral genetic material and slices them to pieces. Here, CRISPR does the same, but with a twist. First, it recognizes portions of the bacteria’s own DNA that code for antibiotic resistance and chops them up. Second, it destroys any viral genetic material that enter the cell. John Timmer, writing for Ars Technica, explains further:

To create this magical construct, the researchers turned to a virus that infects bacteria called λ (familiar to anyone who’s taken a class in gene regulation). λ has a mode of infection in which it inserts itself into the host genome and resides there, dormant until some point in the future. λ was modified so that it would remain dormant indefinitely.

To give this version of λ something that’s useful to bacteria, the authors equipped it with the CRISPR-Cas9 system along with genes for targeting RNAs that would direct it to other viruses. Now, if those viruses tried to infect a cell with the modified λ already in it, they’d be cut to pieces. In essence, they were using a virus to make bacteria immune to another virus. Viral infections went down by three orders of magnitude.

It’s an elegant way to eliminate evolved antibiotic resistance, one which could buy us time to prepare for a possible post-antibiotic world. But even this technique wouldn’t be effective indefinitely. Evolution could stumble upon another route to antibiotic resistance, one that the inserted CRISPR system doesn’t recognize. Then we’d have to deal with bacteria that are both drug- and virus-resistant. Not an ideal combination.