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Pneumonia bacteria invade the body by hijacking proteins that let the germs enter one side of blood vessel cells and travel through them to reach the brain on the other side, according to St. Jude investigators.
The bacteria Streptococcus pneumoniae bind to a membrane protein on blood vessels called PAFr (platelet activating factor receptor), which triggers another cell protein called beta-arrestin 1 to join this pair, according to results of a study published in the December issue of Infection and Immunity. Helped by beta-arrestin, the bacteria-PAFr combination gets “swallowed” by the cell—a process called endocytosis—and folded into a sac called a vacuole. The vacuole then moves through the cell to the side next to the brain.
There, the bacteria escape the vacuole and enter the cerebrospinal fluid around the brain. The St. Jude team showed that the movement of S. pneumoniae across blood vessels was substantially slowed in mice lacking the gene for PAFr, according to Elaine Tuomanen, MD, chair of Infectious Diseases and director of the Infection and Host Defense Program and the Children’s Infection Defense Center. Tuomanen is senior author of the paper.
The investigators also showed that two different parts of the beta-arrestin 1 molecule are linked to endocytosis. One part of the molecule works directly to permit endocytosis. Another part of beta-arrestin 1 is critical to preventing the vacuole carrying the bacteria from being transported to the lysosome—a bag of enzymes in the cell that destroys foreign matter—by triggering a series of biochemical signals called the MAP kinase pathway. This protects the invading bacteria and lets them survive to reach the brain.
“We found that the more beta-arrestin there was in the cell, the more vacuoles were able to avoid lysosomes and transport their bacterial cargo,” Tuomanen said.
Other authors of the paper include Peter Murray, PhD, and Jana Radin, Infectious Diseases; Gopal Murti, PhD, Scientific Imaging Shared Resource; and former St. Jude employees Christopher Guglielmo and Carlos J. Orihuela.
Last update: February 2006