Plague Strain Shrugs Off Antibiotics

A strain of plague-causing bacteria that is resistant to the antibiotics normally used to treat the disease has emerged in Madagascar. Although the researchers who isolated it say they know of no other occurrences of the resistant bacteria, they note that the genes that confer drug resistance can easily spread to other plague strains, posing a threat of new pandemics of the disease.

Transmitted mainly by flea bites, bubonic plague last flared up as a pandemic more than 100 years ago in Hong Kong before spreading around the world. Today, although the disease is still fatal when not treated on time, antibiotics have reduced the mortality rate in plague patients to about 10%.

But in tomorrow's New England Journal of Medicine, a team of researchers from the Pasteur Institutes in Paris and in Antananarivo, Madagascar, reports having isolated a drug-resistant strain of Yersinia pestis, the bacterium that causes plague, from a patient in Madagascar. The patient did not respond to the classical therapy for the disease, a cocktail of the antibiotics chloramphenicol, streptomycin, and tetracycline. Y. pestis isolated from the patient also failed to respond to another antibiotic mix, containing sulfonamides and tetracycline, that is often given to people who may have been exposed to plague. The patient survived, however, thanks to yet another antibiotic, trimethoprim, to which the plague strain was not resistant.

Just how the bacterium manages to outwit the drugs is not yet clear. But the researchers report isolating from the new strain a small, circular strand of DNA, known as a plasmid. Similar plasmids carry the genes for antibiotic resistance in other resistant bacteria, such as enterobacteria and the E. coli that inhabit the gut of humans and other animals. The team showed that in the test tube the plasmid could be transferred from the resistant Y. pestis to both a laboratory strain of the same bacterium and to E. coli. "This transfer [of plasmids] takes place at a high frequency," says team member Elisabeth Carniel of the Pasteur Institute in Paris, which suggests that such antibiotic resistance could easily spread.

David Dennis of the Centers for Disease Control and Prevention in Fort Collins, Colorado, warns that this finding may have international implications: "It is an isolated case, but it sounds a warning that we need to be alert to the possibility that it could spread to other strains," he says. "If it does, that would be a considerable public-health concern."

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