Umeå scientist publishes new findings about origin of plague bacterium

A team including researchers at the Total Defense Research Institute, NBC Defense, in Umeå, Sweden, and the Department of Molecular Biology, Umeå University, are publishing in this week’s issue of Science new findings that show that the protein Ymt is of crucial importance for the capacity of the plague bacterium to survive and spread the plague via flea vectors. Professor Åke Forsberg and visiting researcher Dr. Peter Cherepanov are studying the properties that enable the plague bacterium Yersinia pestis to cause life-threatening infections in animals and humans. Increased knowledge of the mechanisms that Y. pestis exploits to conquer the body’s immune defense can make it possible to develop new methods of treatment for serious infectious diseases.

Historically, the plague is one of our most feared infectious diseases. During the most wide-spread epidemic in the middle ages, also known as the Black Death, more than 25% of the European population died. Today the disease is not very common, with some 2,000 cases per year. The plague occurs primarily in Africa and Asia, but there are also a few cases in North America every year.

The bacteria are normally spread by fleas, first of all to rodents. Humans can also be infected by fleas. When the disease reaches the lungs of a human, the infection can be spread through the air to other people. The onset of the disease is rapid, with a high temperature and a headache. There is often an enlargement of the lymph glands located near the back of the jaw, which explains why it is also called the bubonic plague. Untreated, the infection quickly reaches the blood, leading to general blood poisoning. Mortality for untreated bubonic plague is over 50%. If the infection is spread by the air to the lungs, the course of the disease is even more rapid, and mortality for untreated lung plague is virtually 100%. The high rate of mortality, together with the rapid progression of the disease, places plague bacteria among those considered for use as a biological weapon.

Y. pestis is very closely related to another bacterium called Y. pseudotuberculosis. The plague bacterium evolved from Y. pseudotuberculosis as recently as 1,500 to 2,000 years ago. Y. pseudotuberculosis leads to a relatively mild stomach infection in humans.

The key to the capacity of the plague bacterium to cause fatal infections in humans lies in the differences between the two species of bacteria. The plague bacterium has two movable genetic elements, plasmids, that Y. pseudotuberculosis lacks. On one of these plasmids the research team has identified a gene that codes for a previously described “mouse toxin” that is seen as a major part of the explanation for the high potency of the plague bacterium in causing disease.

The researchers have now shown that the gene, Ymt, is not at all involved in the infection of animals but instead is absolutely crucial to the ability of the bacterium to survive in fleas and thereby to spread the disease further. The ability to spread the disease via fleas represents a decisive step in the development of the plague bacterium. Thus, this ability arose in connection with the acquisition of the plasmid that hosts the Ymt gene.

The Umeå scientists arrived at these findings in collaboration with researchers from the Rocky Mountain Laboratories, NIH, Hamilton, and the University of Michigan Medical School, Ann Arbor, Michigan.