Researchers at Tufts University School of Medicine and the Sackler School of Graduate Biomedical Sciences at Tufts have identified how one type of bacteria, Yersinia, immobilizes the immune system in order to grow in the organs of mice. To do so, the researchers extended the use of a technique and suggest that it could be used to study other bacteria that use the same or similar means of infection. The study is published in the September 11 issue of Cell Host & Microbe.
Led by microbiologist Joan Mecsas, the research team studied a specific member of a family of effector proteins known as Yops. Like other effector proteins, Yops alter the immune system to make it possible for bacteria such as Yersinia to spread in infected organs and from organ to organ. The research team studied the Yop known as YopH in order to identify its specific effect within infected spleens.
Many bacteria inject proteins into cells in organs as a part of their infection process. The technique they used, called the TEM-1 reporter system, uses an enzyme and a dye to color-code cells. This enables researchers to see which of the many cells in an organ have been injected. The current study used the TEM system to identify injected cells but then, in an interesting first, gathered these cells from infected organs to study them further.
After isolating the color-coded cells from infected organs, the researchers determined how immune cells are made inactive by effector proteins, such as YopH and other Yops, by comparing cells with and without the specific effector protein. The research team used tissue samples from two sets of mice with Yersinia pseudotuberculosis: those with and without functional YopH proteins. They separated tissue cells from immune cells taken from spleens and compared suspended immune cells from the two sets of mice.
The researchers determined that YopH deactivates multiple proteins and blocks calcium flows vital to normal immune cell communication. Decreased immune cell communication allows Yersinia to continue spreading in infected organs without an effective response from the immune system.
"Being able to pull out and study cells from infected tissues that contain bacterial proteins enabled us to see the effects of YopH in tissues infected with Yersinia pseudotuberculosis. Our application of this technique may also work in bacteria similar to Yersinia, to understand how other bacteria cause damage in organ systems," said senior author Joan Mecsas, Ph.D., an associate professor of molecular biology and microbiology at Tufts University School of Medicine and member of the immunology and molecular microbiology programs at the Sackler School of Graduate Biomedical Sciences at Tufts.