How Flesh-Eating Bacteria Attack the Body’s Immune System

The research focuses on the major human pathogen group A Streptococcus. Among the most important of all bacterial pathogens, strep is responsible for a wide range of diseases – from simple strep throat to life-threatening conditions such as necrotizing fasciitis (“flesh-eating disease”) and toxic shock syndrome.

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, MD, 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.”

The critical role of the strep protease was confirmed by cloning the corresponding gene into a normally non-pathogenic bacterial strain, which then became resistant to neutrophil killing. More detailed analysis demonstrated that by inactivating IL-8, SpyCEP blocked neutrophil migration across blood vessels as well as neutrophil production of "extracellular traps" used to ensnare bacteria.