Skip Ribbon Commands
Skip to main content
Translate
Translate
menu iconMenu
search iconSearch

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

 

August 13, 2008  |   

“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. The finding, which could aid in development of new treatments for serious infections in human patients, will be reported in the August 14 issue of the journal Cell Host & Microbe.

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. 

“These findings may suggest a new approach to treating serious Strep infections by supporting our body’s natural defense system,” said Nizet.

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, 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.”

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.

The immune-blocking effects of SpyCEP produced by Strep were strong enough to allow other bacterial species to survive at the site of infection, which may contribute to mixed infections that require complex antibiotic regimens. The researchers also showed that a pathogen of fish, Streptococcus iniae, produces its own version of SpyCEP that may contribute to recent reports of severe skin infections caused by this bacterium in fish handlers.

Nizet explained that the researchers' findings could lead to novel treatments for Strep-related diseases.  “In addition to attempting to kill the bacteria directly with standard antibiotics, new treatment strategies could be targeted to inhibit the Strep protease and thereby disarm the pathogen, making it susceptible to clearance by our normal immune defenses,” he said.

This study was financed by grants from the National Institutes of Health and the Swiss National Science Foundation. Co-authors contributing to the study were Anjuli Timmer, Ph.D., Jeffrey Locke, Ph.D., and John Buchanan, Ph.D., of the UCSD Department of Pediatrics; Morgan Pence, UCSD graduate student in biomedical sciences; Claire Turner and Shiranee Sriskandan, Ph.D., of Imperial College, London; and Inbal Mishalian and Emmanuel Hanski, Ph.D., of the Hebrew University in Jerusalem.

# # #

Media Contact: Debra Kain, 619-543-6163, ddkain@ucsd.edu



Media Contact

Related News

4/22/2015
UC San Diego Health System and Scripps Health are partnering to provide improved continuity of patient care, fellowship training and research in hospice and palliative medicine. Under a new five-year ...
4/20/2015
Researchers at the University of California, San Diego School of Medicine and Moores Cancer Center have discovered a molecular mechanism that connects breast tissue stiffness to tumor metastasis and p ...
4/20/2015
A decrease in the amount of time spent eating and an increase in overnight fasting reduces glucose levels and may reduce the risk of breast cancer among women, report University of California, San Die ...
4/20/2015
The threat of falsified medications, also referred to as counterfeit, fraudulent, and substandard, can be quite real, yet the full scope and prevalence of the problem is poorly understood, say researc ...
4/17/2015
Researchers at the University of California, San Diego School of Medicine have created an in vitro, live-cell artificial vessel that can be used to study both the application and effects of devices us ...
4/16/2015
The increase in use of e-cigarettes has led to heated debates between opponents who question the safety of these devices and proponents who claim the battery-operated products are a useful cessation t ...
4/16/2015
An international team of scientists, led by researchers at University of California, San Diego School of Medicine, have found genetic overlap between Alzheimer’s disease (AD) and two significant cardi ...
4/13/2015
About one quarter of all atrial fibrillation patients at the lowest risk for stroke receive unnecessary blood thinners from cardiology specialists, according to a new study by researchers at Universit ...