The bacteria responsible for the plague and some forms of food poisoning "paralyze" the immune system of their hosts in an unexpected way, according to a new study in the September 8, 2006 issue of the journal Cell.
The researchers found that these bacteria, which belong to the genus Yersinia, harbor a protein that mimics an apparently unrelated mammalian enzyme. That copycat protein blocks host cells' capacity to change shape and move, abilities important for cells of the immune system to track down and "eat" foreign invaders, the researchers explained.
The discovery marks the second way in which this protein, called YpkA, compromises the immune system. Earlier studies suggested that another portion of YpkA--which may have been derived from a mammalian enzyme and later co-opted by Yersinia--has activity that also influences cell shape by a separate, though incompletely understood mechanism.
The findings offer important new insight into the factors that lend Yersinia their ability to spawn disease, the researchers said. The results might also contribute to new strategies for fighting the bug.
"Yersinia injects several virulence factors into its host," said C. Erec Stebbins of Rockefeller University. "If we can discover which ones are critical, we might identify the pathogen's Achilles heel--an attractive target for antibacterial or anti-virulence compounds."
"We were quite excited to see such a critical and unexpected factor in the virulence of Yersinia--a bacteria historically responsible for some of the worst diseases," he added. Although improvements in sanitation have eliminated acute problems from diseases caused by Yersinia, concerns remain about the possibility that an untreatable strain might arise or that the bacteria might come into use as a biological weapon, he said.
Nearly 200 million people are estimated to have died in the plague epidemics that devastated the ancient world, the researchers said. The successful weaponization of plague in the former Soviet Union bioweapons program also made the pathogen a primary biodefense concern. Additional medical concerns have arisen from the evolution of multidrug-resistant strains of the plague bacterium found in patients from several locations.
The plague bacterium Yersinia pestis is closely related to Y. enterocolitica and Y. pseudotuberculosis, which are food-borne agents that cause inflammation of the stomach and intestines. All Yersinia bacteria have a virulence plasmid, which is necessary to cause disease. Plasmids are extra DNA molecules frequently found in bacteria containing genes that can be passed from one bacterial strain to another and that may confer an evolutionary advantage, such as antibiotic resistance.