“Flesh-eating” or “Strep” bacteria are able to survive and spread in the body by degrading a key immune defense molecule, according to researchers at the University of California, San Diego, School of Medicine and Skaggs School of Pharmacy and Pharmaceutical Sciences.
Led by senior author Victor Nizet, M.D., UC San Diego professor of pediatrics and pharmacy and an infectious diseases physician at Rady Children’s Hospital, San Diego, the researchers showed that a protease known as SpyCEP (Strep. pyogenes cell envelope protease) – produced in large amounts by the most dangerous strains of Strep –inactivates an immune system molecule that controls the body’s white blood cells ability to fight bacteria. Without signals from this molecule, white blood cells become slower and weaker, and infections can spread out of control.
The UC San Diego investigators examined the interaction of Strep bacteria with neutrophils, specialized white blood cells that play a front-line role in humans’ immune defense against pathogenic microbes. Previous research had shown that Strep bacteria change their pattern of gene expression dramatically during the course of infection, including a massive increase in production of SpyCEP, which has the unique ability to inactivate an immune defense molecule known as interleukin-8 (IL-8). IL-8 is produced at sites of infection and serves as a signal for neutrophils to migrate out of the bloodstream and into the tissues to clear the infection.
The UC San Diego team used a molecular genetic approach for their studies, knocking out the gene encoding the SpyCEP from a pathogenic strep strain that was originally isolated from a patient suffering from necrotizing fasciitis.
“Lacking this single protease, the mutant Strep strain was easily killed by human neutrophils,” said lead author Annelies Zinkernagel, M.D., a postgraduate researcher in the UCSD department of pediatrics. “In addition, the mutant Strep bacteria no longer produced a spreading infection when injected into the skin of experimental mice.”
Release date: August 13, 2008
Source: University of California – San Diego
