Editing the sequence of bases in a DNA molecule is pretty straightforward in a test tube. Until recently, editing the DNA of a living organism had been a very large challenge, one that was more often avoided than taken up. But a system bacteria use to defeat viruses has been repurposed to make a versatile DNA editing system.

The system, called CRISPR-Cas9, takes short pieces of RNA as input. Any places it spots the same sequence in a DNA molecule, it makes a cut. Those cuts will then generally be repaired using any DNA sequence that roughly matches it. If researchers provide an edited version of the sequence, then the edits get incorporated into the cut DNA.

The system made news recently when it was used to edit the DNA of fertilized human embryos. But it's seen plenty of other uses, from targeting HIV infections to creating a mutagenic chain reaction that can spread through populations of pests. Now, some researchers have turned it against another threat: antibiotic resistance.

It's not an obvious thing to target. Editing the DNA of bacteria involves getting DNA inside populations of bacterial cells in settings like hospitals. The most convenient way to do that is with a virus. And, if you're going to target bacteria with a virus, you might just as well use a virus that kills them, right?

Yes and no. Having a killer virus simply selects for bacteria that can resist infection, setting off an evolutionary arms race between the bugs and the virus. Meanwhile, the problem of antibiotic resistance is still with us.

So, some researchers at Tel Aviv's Sackler School of Medicine came up with a clever idea: why not create a virus that gives bacteria something that's useful to them, but gets rid of antibiotic resistance at the same time? Under normal growth circumstances, the bacteria would readily pick up the virus, because it's useful. But, when faced with an antibiotic assault, they'd be helpless to resist it.

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.

To make it useful to us, the researchers added a second set of genes for targeting RNAs. These directed the CRISPR-Cas9 system to cut up antibiotic resistance genes. This worked as expected: λ infected cells couldn't pick up the antibiotic resistance genes and, if they had any before the infection, they were lost. The bacteria remained susceptible to antibiotics.

So, in theory, wiping out antibiotic resistance in a hospital setting could be as simple as spraying the engineered λ virus, along with whatever virus it provides resistance to. In fact, if you engineered a virus that did several useful things for the bacteria, it could become possible for it to spread through wild populations via horizontal gene transfer.

That's the good news. The bad news is that it should be possible for evolution to modify the λ in a bacterial genome so it maintains its viral resistance abilities, but loses its ability to wipe out antibiotic resistance. In addition, λ only infects E. coli, and there are strains of that bacteria that are already resistant to it. Targeting other significant disease-causing bacteria will be a challenge.

Still, it's a creative approach that could pay dividends in some contexts. And it's possible that other researchers will figure out ways of extending the approach so it's more widely effective.

PNAS, 2015. DOI: 10.1073/pnas.1500107112 (About DOIs).