Will the Plague Pathogen Become Resistant to Antibiotics?

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.

The paper appears in the March 21 issue of PLoS ONE, the international, peer-reviewed, open-access, online publication from the Public Library of Science (PLoS). After publication, the paper will be available on the PLoS ONE site (www.plosone.org) and at http://dx.doi.org/10.1371/journal.pone.0000309.