News & CommentMicrobiology

# New Hunt for the Roots of Resistance

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Science  03 Apr 1998:
Vol. 280, Issue 5360, pp. 27
DOI: 10.1126/science.280.5360.27

As bacteria worldwide acquire resistance to the drugs meant to kill them, public health experts have stepped up surveillance of antibiotic resistance in human pathogens. Now a grassroots network of scientists is taking aim at what they see as the root of the problem: resistance genes in harmless bacteria that live in humans, animals, plants, even soil and water. By keeping tabs on when and where specific antibiotic-resistance genes appear, the group hopes to predict—and one day help block—the spread of resistance.

Efforts to track resistance in clinical pathogens have “too narrow a focus,” argues Abigail Salyers, a microbiologist at the University of Illinois, Urbana-Champaign, who helped organize a meeting in Boston last week to plot the new strategy. She explains that antibiotic resistance can hide undetected in harmless bacteria well before it shows up in patients. “Clinical isolates are the tip of the iceberg compared to what's out there in the environment,” agrees microbiologist Stuart Levy of Tufts University School of Medicine, who is president-elect of the American Society for Microbiology (ASM) and president of the Alliance for the Prudent Use of Antibiotics (APUA), an international group that hosted the Boston meeting.

Seemingly harmless bugs are worth watching, Levy says, because widespread dosing of both humans and animals with antibiotics selects for drug resistance in benign bacteria that normally thrive in such places as the large intestine. The resistance genes can then jump species lines into disease-causing bacteria. When that happens, the genes from harmless bugs are anything but. For example, ampicillin has lost its potency against infections caused by Haemophilus influenzae because the bacterium picked up an ampicillin-resistance gene from Escherichia coli in the 1970s. The ASM estimates that drug-resistant pathogens cost more than $4 billion per year in extra medical costs in the United States alone. By using sequence similarities in resistance genes from different bacteria as an indicator, scientists have already identified a handful of such trans-species leaps, although they can't prove which way the genes jumped (see table). View this table: To provide early warnings of such gene transfers, the new network will catalog resistance gene sequences and data on specific strains in a searchable Internet database. The 19-member working group hopes to enlist scientists, physicians, and public health workers worldwide, reaching them through the existing networks of the 7000-member APUA and the 40,000-member ASM, as well as with editorials in scientific journals. Funded by a$100,000 National Institutes of Health grant, the group will also launch two pilot studies. One study will compare drug resistance in harmless gut bacteria from rural Mexican children, who have not been exposed to antibiotics, with bacteria from children in Mexican cities, where antibiotics are sold over the counter. The other study will compare resistance in gut bacteria from antibiotic-fed cattle with those from antibiotic-free bison.

Not everyone agrees that these efforts are on the right track. The link between resistance in harmless bacteria in animals and in human pathogens is “pretty tenuous,” says Richard Carnevale, director of regulatory affairs at the Animal Health Institute, a group that represents producers of animal antibiotics. “I'm not sure it's worth doing.” But other experts support the undertaking. “Their approach is the correct one,” says microbiologist Mark E. Jones of MRL Reference Laboratories, who directs resistance surveillance efforts in Europe.

As drug-resistant pathogens continue to emerge from the shadows, researchers are eager to start their hunt. Says Salyers: “We need the answers yesterday.”

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