Scientists Discover New Way for Antibiotic Resistance to Spread

Washington State University researchers have found an unlikely recipe for antibiotic-resistant bacteria: Mix cow dung and soil, and add urine infused with metabolized antibiotic. The urine will kill off normal E. coli in the dung-soil mixture. But antibiotic-resistant E. coli will survive in the soil to recolonize in a cow's gut through pasture, forage or bedding.

"I was surprised at how well this works, but it was not a surprise that it could be happening," says Doug Call, a molecular epidemiologist in WSU's Paul G. Allen School for Global Animal Health. Call led the research with an immunology and infectious disease PhD student, Murugan Subbiah, now a post-doctoral researcher at Texas A & M. Their study appears in a recent issue of the online journal PLOS ONE.

While antibiotics have dramatically reduced infections in the past 70 years, their widespread and often indiscriminate use has led to the natural selection of drug-resistant microbes. People infected with the organisms have a harder time getting well, with longer hospital stays and a greater likelihood of death.

Animals are a major source of resistant bugs, receiving the bulk of antibiotics sold in the U.S.

The scientists focused on the antibiotic ceftiofur, a cephalosporin believed to be helping drive the proliferation of resistance in bacteria like Salmonella and E. coli. Ceftiofur has little impact on gut bacteria, says Call. "Given that about 70 percent of the drug is excreted in the urine, this was about the only pathway through which it could exert such a large effect on bacterial populations that can reside in both the gut and the environment," he says.

Until now, conventional thinking held that antibiotic resistance is developed inside the animal, Call says.

"If our work turns out to be broadly applicable, it means that selection for resistance to important drugs like ceftiofur occurs mostly outside of the animals," he says. "This in turn means that it may be possible to develop engineered solutions to interrupt this process. In doing so we would limit the likelihood that antibiotic resistant bacteria will get back to the animals and thereby have a new approach to preserve the utility of these important drugs."

One possible solution would be to find a way to isolate and dispose of residual antibiotic after it is excreted from an animal but before it interacts with soil bacteria.

The WSU experiments were performed in labs using materials from dairy calves. Researchers must now see if the same phenomenon takes place in actual food-animal production systems.

Infection Control Today

Will The Plague Pathogen Become Resistant To Antibiotics?

Will The Plague Pathogen Become Resistant To Antibiotics?
Mar 21 2007

Science Daily — A small piece of DNA that helps bacteria commonly found in US meat and poultry resist several antibiotics has also been found in the plague bacillus Yersinia pestis, gene sequence researchers report.

The ability to resist many of the antibiotics used against plague has been found so far in only a single case of the disease in Madagascar. But because the same ability is present in other kinds of bacteria from a broad range of livestock, antibiotic resistance could potentially spread to other Y. pestis and also other bacterial pathogens. In a paper published March 21 in the new journal PLoS ONE, the authors say this possibility "represents a significant public health concern."
Genetic ability to disable antibiotics, including multidrug resistance (MDR) sequences, is carried on plasmids, small circles of DNA that are passed easily between bacteria. In this study, the same MDR plasmids found in the Y. pestis from Madagascar were also present in bacteria such as Salmonella and Escherichia coli found in retail samples of beef, pork, chicken, and turkey from several US states.

"What we've done is revealed a mechanism for the acquisition of multidrug resistance in Y. pestis. Obviously, this is an event that might have serious human health consequences. But the sequencing work we've done has given us a way to monitor this plasmid in future," says senior author Jacques Ravel of The Institute for Genomic Research (TIGR) in Rockville, MD.
"The fact that we found a plasmid usually found in Salmonella in Y. pestis is a big problem. It also raises a question about how this happened, how it went from one to the other. But that's a question we cannot answer in this paper," Ravel notes. He urges a new monitoring program to track MDR in Y. pestis.

MDR Salmonella and E. coli have been found in droppings from wild geese, raising the possibility that wild animals might be able to spread MDR far beyond the livestock where it originated, Ravel notes.

"When we identified the first Y. pestis strain resistant to multiple antibiotics, we warned that if this type of strain spreads or emerges again, it would pose a serious health problem" says co-author Elisabeth Carniel, head of the Yersinia Research Unit at the Institut Pasteur in Paris. "The discovery that the multiresistance plasmid acquired by the plague bacillus is widespread in environmental bacteria reinforces this warning".

There have been many plague epidemics in human history, and Y. pestis is believed to have killed an estimated 200 million people. Plague is now regarded as a re-emerging disease, with small outbreaks all over the world. Because plague is often fatal, Y. pestis is a potential agent for bioterrorism. There is no vaccine, but antibiotics are useful for treatment and for preventing the disease's spread. The researchers observe, "Our data imply that high levels of MDR in the causative agent of plague may rapidly evolve naturally, and present a vital biomedical, public health, and biodefense threat."

The paper resulted from an international collaboration among researchers at TIGR, a division of the J. Craig Venter Institute, the Institut Pasteur in Paris, the Agricultural Research Service of the US Department of Agriculture, and the US Food and Drug Administration. This work was performed at the National Institute of Allergy and Infectious Diseases-funded Microbial Sequencing Center managed by TIGR.

Citation: Welch TJ, Fricke WF, McDermott PF, White DG, Rosso M, et al (2007) Multiple Antimicrobial Resistance in Plague: An Emerging Public Health Risk. PLoS ONE 2(3): e309. doi:10.1371/journal.pone.0000309

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