Probiotic shows promise in tackling C.difficile
Scientists at the University of Wisconsin-Madison are working on an edible version of the CRISPR gene-editing tool to help eliminate bacteria such as Clostridium difficile in a targeted way. A team led by Jan-Peter van Pijkeren is developing a probiotic cocktail that includes a bacteriophage, a virus that in this case sends C.difficile bacteria a false message which prompts it to make cuts to its own DNA. Pijkeren concedes that the technology is in its very early stages, however, experts have said a "CRISPR pill" could become a "complementary tool" in the fight against bacterial infections. C.difficile has been ranked by the US Centers for Disease Control and Prevention as the top drug-resistant threat.
CRISPR is the powerful gene-editing technology already being explored as a way to precisely edit human genes to cure diseases (see "Can CRISPR Save Ben Dupree?"). But the technology’s versatility is such that it’s being studied for a huge range of other uses. Just last week scientists in Boston showed they could craft CRISPR into cheap, simple diagnostic tests.

Now scientists want to turn it into ultra-precise antimicrobial treatments to “specifically kill your bacteria of choice,” says food scientist Jan-Peter Van Pijkeren of the University of Wisconsin-Madison.

While not a household name, Clostridium difficile tops the U.S. Centers for Disease Control and Prevention’s list of urgent drug-resistant threats. A 2015 study by the agency found that the bug caused nearly half a million infections in Americans, including 15,000 deaths.

CRISPR was actually discovered in bacteria. In fact, the system is an immune defense bacteria use to fend off invading viruses called bacteriophage.

The way it works is that bacteria store memories of viral DNA in their own genomes as “clustered regularly interspaced short palindromic repeats”—or CRISPRs. They use this memory, plus a DNA-slicing enzyme known as a Cas to recognize and chop up the genes of invading bacteriophage.

Van Pijkeren’s idea is to use bacteriophage to send a false message to C. difficile, one that instead causes the bacteria to make lethal cuts to its own DNA.

To do it, Van Pijkeren lab is developing bacteriophage capable of carrying a customized CRISPR message. On their own, the bacteriophage would quickly get broken down by stomach acid. So to get the viruses into a person, Van Pijkeren plans to add them to a cocktail of innocuous bacteria, or probiotic, that a person could swallow as a pill or a liquid.

Van Pijkeren compares the probiotic to a “mothership.” As the probiotic bacteria pass through a person’s intestinal tract, the bacteriophage would burst forth and infect any nearby C. difficile, causing them to hack up their own DNA.