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NDM-1: A New Superbug

In the fight against a burgeoning breed of drug-resistant pathogens, researchers look to add weapons beyond antibiotics.

By Brandon Keim // Spring 2011
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Leif Parsons

A superbug with a new drug-resistance gene: That’s how the popular press often describes New Delhi metallo-beta-lactamase, NDM-1 for short. The more accurate description is even more troubling, because NDM-1 contains a slew of drug-resistance genes, including one that blocks carbapenems, a widely used class of antibiotics and currently one of the few last-ditch defenses against many drug-resistant pathogens. Even nonantibiotic approaches under study, as Proto described in the Fall 2008 issue (“The War on Superbugs”), are unlikely to defeat the bug anytime soon.

NDM-1’s arsenal of drug-resistance genes includes a group on a DNA segment called a transposon. Also called jumping genes, transposons tend to detach en masse from their chromosome and fuse with another one, sometimes after picking up pieces of free-floating DNA called plasmids.

Transposons and plasmids allow a bacterium to adapt rapidly, exchanging genes between individuals and species quickly. In the case of NDM-1, they allow any member of the Enterobacteriaceae family—a large group that includes Escherichia coli as well as bugs that can cause pneumonia and plague—to become a superbug. “Because it has a whole string of resistance genes, there’s hardly any drug left to treat the disease,” says Robert Moellering, a Harvard Medical School specialist in the evolution of antibiotic resistance. “Some of these strains are resistant to everything.”

In addition to Klebsiella pneumoniae, NDM-1 has insinuated itself into E. coli, Enterobacter and Morganella, all common sources of human infection. In New Delhi—the densely populated center of the region from which NDM-1 has spread to North America, Europe, South America and Australia—a recent survey of community sewage and drinking water found NDM-1 to be widespread and present in no fewer than 11 bacterial species.

To fight back against the entire advancing army of drug-resistant bugs, researchers are experimenting with nonantibiotic approaches, such as defusing the proteins that make pathogens toxic. In theory, those approaches might work against NDM-1, but they’re still at very early experimental stages.

Among researchers and public health experts who study drug resistance, the sense of alarm is palpable. “The whole issue deserves massive urgency,” says University of British Columbia microbiologist Bob Hancock, whose work is focused on bolstering the body’s innate immunity against bacteria. “It takes 15 years to develop a drug. Just extrapolate the curves we’re seeing for any antibiotic resistance out to 15 years, and the situation looks extremely grim.”

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