Protecting against a difficult microbe

From Toronto, at a meeting of the Infectious Diseases Society of America

A team of scientists has devised a vaccine against Clostridium difficile by using the bacterium’s DNA. Although the researchers so far tested the approach only in mice, the results could open a new line of attack against the bacterium, which has grown increasingly resistant to antibiotics in the past 5 years.

The researchers started with C. difficile’s gene for a toxin that causes diarrhea, fever, and abdominal pain. They then altered the gene so that it would enter human cells and there make a harmless fragment of the toxin. “It’s like translating the DNA into a language the mammalian cells can understand,” says study coauthor David F. Gardiner, an infectious-disease physician at the Weill Medical College at Cornell University in New York City.

To get the altered gene into mice cells, the team applied mild electrical stimulation to the animal’s skin after injecting the synthetic gene. “That polarizes the cell and moves the DNA into it,” says Gardiner.

The cells secreted the toxin fragment, which drew the attention of the animal’s immune system, Gardiner explains. The mice then manufactured antibodies geared toward neutralizing the toxin.

When exposed to drug-resistant C. difficile, all animals receiving the DNA vaccine survived, whereas all members of another group that received inert shots died within a day, Gardiner reported.

Resistant strains of C. difficile were responsible for 7,000 cases of illness in Quebec hospitals in 2003. Such strains have plagued other hospitals as well (SN: 2/18/06, p. 104: Flora Horror).

The strain of C. difficile used in this study accounts for about 80 percent of the disease caused by this microbe in the United States, Gardiner says. Next, the researchers plan to test the DNA vaccine in hamsters, which are more like people in their reaction to C. difficile toxin than mice are.

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